New Info for COVID-19: Immune Response, Vaccine Development, & Asymptomatic Infections
by
Columbia University Professor Emeritus, Dr. David Figurski
presented by
Donna O’Donnell Figurski
(Disclaimer: The World Health Organization <WHO> has officially named the new coronavirus as SARS-CoV-2 and the disease it causes as COVID-19. Because the majority of people, including much of the press, commonly refers to the virus as “COVID-19,” to avoid confusion I use COVID-19 as the name of the virus in these posts.)
David H. Figurski, Ph.D & Survivor of Brain Injury
I have taken a 119-minute podcast on COVID-19 by a virologist and reduced it to the 21 minutes you probably want to hear the most. This long post looks scary, but it’s actually very easy to read and makes the 21 minutes readily understandable.
Dr. Vincent Racaniello, a virologist at Columbia University, was my colleague in the Department of Microbiology & Immunology. He does a podcast on viruses, called TWiV (This Week in Virology). Since March 13th, when we started staying home and taking precautions to minimize the pandemic, Vincent has released over 40 podcasts, nearly all of which are about COVID-19.
TWiV is unique because the host, Vincent, does research on and lectures about viruses. In addition to his being a scientist, his podcasts always have a panel of PhDs, sometimes as many as five people (two more virologists, an immunologist, a parasitologist, and a former student – now a science reporter). The discussions are great and done with a non-scientist-audience in mind. TWiV is known worldwide and attracts tens of thousands of listeners every month. However, the TWiV podcasts are long (~1-2.5 hours), so I listen and tell you the minutes to listen to hear information that I think you’ll want to know. 
This post is about TWiV #631, which was posted on June 25, 2020. (Note: The TWiV link is for all the podcasts. Be sure you listen to #631.)
TWiV podcast #631 is 119 minutes long, but I have selected ~21 minutes you may want to hear. The topics you’ll hear discussed are the following: the value of the safety precautions, the need for free and extensive testing, the unknowns of the immune response, the timetable for vaccine development (at least eight more months), and the role of age in symptomatic and asymptomatic infections.
I have broken down #631 into segments defined by the minutes I chose for you to listen to. (The last half of the podcast was spent answering questions from listeners. While much good information is in this section, I emphasized the parts you probably want to hear the most.) 
Podcast #631 features a discussion by three scientists: Vincent (virologist, professor, Columbia U.), Rich Condit (virologist, Professor Emeritus, U. of Florida), and Brianne Barker (immunologist, professor, Drew U.). The scientists usually make sure their discussion is understandable to their generally non-scientist listeners, but I found that they occasionally used terms that may be unfamiliar to you. Therefore, I have provided a glossary in the segment in which the term is first used.
TWiV #631
Segment 1
Minutes 3:10-9:10
The cavalier attitude of some people to safety precautions; the spike of new cases in the US; the toxic mixture of politics and science; the 172 vaccine projects planned or in progress; how vaccine development – done properly – will take over eight more months
glossary
rotavirus – common RNA virus responsible for diarrhea in young children and infants. Worldwide, the virus is responsible for as many as 400,000 deaths annually. A vaccine was introduced in 2006.
protein subunit-based – Some large proteins are actually complexes of individual proteins or “subunits.” Inactivation of an essential subunit (for example, by a vaccine) inactivates the whole protein complex.
Phase III clinical trial – Clinical development of a vaccine is a three-phase process. During Phase I, small groups of people receive the trial vaccine. In Phase II, the clinical study is expanded and the vaccine is given to people who have characteristics (such as age and physical health) similar to those for whom the new vaccine is intended. In Phase III, the vaccine is given to thousands of people and tested for efficacy and safety. (from the CDC)
Segments 2 and 3
Minutes 17:20-19:05 and 22:25-24:00
Possible importance of T cells in the immune response; the role of antibodies may not be as important as first thought; implications
glossary
antibody – part of the adaptive immune response (see “innate immunity” below), which eventually selects for proteins (antibodies) that specifically bind to foreign (usually) substances (like viral proteins). Binding of an antibody to a substance can cause inactivation of that substance.
serology – the analysis of blood for the presence of antibodies that bind specific substances (in this case, to proteins of COVID-19). A positive serology test for COVID-19 means that you are now infected or have been infected sometime in the past.
T and B cells – The white blood cells are important to the immune response. Several types of white blood cells have been identified. T cells and B cells are two major classes. B cells produce antibodies. Two subtypes of T cells are known to be important for the immune response to COVID-19. One subtype signals B cells to produce antibodies. Another subtype (cytotoxic T cells) kill virus-infected cells. The scientists discuss the evidence that the latter subtype of T cells may be very important to the immune response to COVID-19.
innate immunity – the first line of defense or the non-specific arm of the immune response. The innate immune response is in contrast to the adaptive (specific) immune response, which includes antibody production and takes days to develop.
PI – Principle Investigator; the head of the project
neutralizing antibody – an antibody that blocks infection by the virus; for COVID-19, an antibody that inactivates the spike protein of the virus (see below) is a neutralizing antibody
IgG – Immunoglobulin Gamma; the majority of the long-lived antibodies in the blood
immunopathology – that part of a disease that is caused by the immune response
Segment 4
Minutes 26:25-29:40
Which vaccine will be the best? What should we think of a vaccine based on spike protein only?
glossary
MHC – Major Histocompatibility Complex – several genes that code for a large set of proteins that are on the surface of every cell. T cells monitor what the MHC surface proteins are bound to. Fragments of proteins (see “peptide” below) are bound to MHC proteins and displayed to a T cell by cell-cell contact. If a cytotoxic T cell recognizes the fragment as normal or “self,” it takes no action. If the cytotoxic T cell “sees” a peptide as different or foreign (as in a virus-infected cell), it will kill the cell. This is part of the innate immunity arm. Stimulation of a T helper cell by an MHC protein bound to a foreign peptide will signal the adaptive arm of the immune response, which includes antibody production.
peptide – a small fragment of a protein
antigen – a substance that stimulates the production of antibodies to itself and molecules very similar to itself. COVID-19 vaccine production uses one or more viral antigens to trigger an immune response in the absence of infection by the virus.
spike protein – a protein of COVID-19; important because it’s needed for the virus to bind tightly to the ACE2 (angiotensin converting enzyme 2) protein that’s on the surface of lung cells; the binding is needed for the virus to gain entry to the cell and start the infection; a target for some vaccines; antibodies that inactivate spike are called “neutralizing antibodies.”
attenuated – An inactivated virus is a virus that’s been killed. An attenuated virus is a live virus that replicates and induces the immune response the natural way, but no longer causes disease. The Salk polio vaccine is based on killed virus. The Sabin vaccine is based on an attenuated polio virus. (Interesting note: Vincent Racaniello sequenced the chromosomes of the normal and Sabin polio viruses and identified three mutations in the Sabin virus.)
Zika virus – a mosquito-borne virus that was first identified in Uganda in 1947 in monkeys. It was later identified in humans. In most cases, there are no symptoms. Most frighteningly, in pregnant women, it may cause subsequent birth defects, including microcephaly (small head due to an undeveloped brain). In early 2015, a widespread epidemic, caused by the Zika virus in Brazil, spread to other parts of South and North America. There’s no vaccine or specific treatment. (from WHO and Wikipedia)
Segments 5, 6, and 7
Minutes 29:55-36:45, 40:45-41:30, and 43:00-43:30
A paper by scientists in Italy provides data from a large pool of people to show that it’s easy to become infected by contact with an infected person, even though the infected person may have no symptoms, and also to show that the greater a person’s age is, the higher is the likelihood of having COVID-19 symptoms. (Seventy-four percent of people under 60 were asymptomatic!)
glossary
PCR-positive – The test for infection is the rapid and convenient PCR (polymerase chain reaction) test. It detects the RNA chromosome of the virus. A PCR-positive result is taken as evidence that the person tested currently has an infection. (But, the test is so sensitive that it can sometimes detect fragments of viral RNA in a recovered patient.)
sero-positive – A positive result in a serology test of a blood sample indicates the presence of antibodies to proteins of COVID-19. The virus does not need to be present for a person to be sero-positive. Such a result indicates that the person is currently infected or was infected in the past.
Stay Safe and Healthy!
Clip Art compliments of Bing.)
(Photos compliments of contributor.)
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A legitimate way for the large Phase III clinical trial to end early is when the benefit is obvious. For example, if a vaccine candidate were given to 20,000 people and a placebo were given to another 20,000 people, the efficacy of the vaccine would be obvious (and statistically sound) if several hundred people in the placebo group became sick, while no person in the vaccine group became sick. Such an obvious result is exceedingly rare, and so, since it normally takes about eight months to do a Phase III clinical trial, if all goes well, we probably won’t have a confidence-inspiring vaccine until 2021.
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