Kiki’s Comments May 2020
TWiV 616: Singing About Coronavirus
Key Points:
*Moderna mRNA Vaccine trial is heading into Phase II after a promising Phase I trial
*airflow and classroom size are factors that should be considered when looking at the classrooms and designing how we go back to in-person teaching
*some instruments are more likely to spread viral infection due to droplet spray
*we need to mitigate and protect the most susceptible people going forward, while trying to keep it manageable for our healthcare systems as we begin to open: TETRIS, hand-washing, masks, and being prepared for another quarantine period
General Comments:
*literature mining search tools: there are a lot of papers being produced and published right now, so it can be difficult to keep up with the literature, to find what specific pieces, and to be able to verify accuracy and quality of the research. There are tools like data mining (e.g. Johns Hopkins Database) that can help with this using human work or algorithms. This may not be the solution for everyone, but can be useful.
*Moderna’s Phase I mRNA Vaccine Trial: the Phase I trial is a safety trial with not many people. It is open label meaning that they know which people get what drugs. Moderna is trying a lipid nanoparticle encapsulating mRNA encoding a pre-fusion form of the spike. This means it has some amino acid changes such that it does not get cleaved in the cell. Ideally this will rearrange it into a form that would probably not be good for blocking antibodies. This will be injected into the muscle of recipients. Cells will take this up and this will be translated in the cytoplasm into the spike protein. They are measuring whether or not the tested individuals will make antibodies in response that are able to neutralize the virus, evaluated using a plaque assay. After two doses of 25mg it looks like there is a level of neutralizing antibody against CoV-2 that is similar or greater to those seen in recovered COVID-19 patients. FDA has cleared Moderna to move this vaccine into Phase II trial, where it will also be testing a higher dosage (50mg dose).
n.b. neutralizing antibody alone may not be enough to give protection. The cellular response may be important for neutralizing infection (i.e. both arms of the immune system may be involved).
*pre-proof: this is a peer-reviewed and accepted article that has not been properly formatted yet.
Papers:
*Dev Cell Smoking and ACE2: In a subset of cells in the respiratory tract, chronic smoke exposure increases the secretory cell population and ACE2 production. Once smoking stops the ACE2 goes down in response. ACE2 may be an interferon stimulating gene (ISG). It is possible that the CoV-2 infection could use a positive feedback loop to increase ACE2 levels.
Questions:
*Mason: does classroom airflow effect viral transfer and spread? The answer to the larger question about transmission will depend on spread (aerosol vs droplet vs direct transfer) of CoV-2. Airflow transfer is a reasonable factor to keep in mind with transmission of infectious disease in any case. No matter what, it will probably be necessary to stagger classes, reduce ratio of people to room size, and have everyone wear masks.
*Sharon: what is the use of Maraviroc for COVID-19? Maraviroc is an HIV antiviral that blocks the coreceptor CCR5, so it is an entry blocker. CCR5 is a chemokine receptor, so we do not know how that would effect CoV-2. So far we do not know of papers that have discovered a beneficial therapeutic use in COVID-19 for Maraviroc.
By Kiki Warren (https://www.linkedin.com/in/kikiwarren/)
