Kiki’s Comments                                                                                                        July 2020

                        TWiV 641: Dr. Anthony Fauci

Key Points:

*droplet transmission may account for the majority of transmission, but it is likely aerosols play a part

*cycle thresholds of 35 or more likely indicate an individual is no longer shedding replication competent virus

*PCR-able versus replication competent survival of the virus on surfaces should be taken into account; it is possible to PCR and detect the virus after it is no longer able to infect and replicate

*asymptomatic and pre-symptomatic transmission is likely substantial

*return to schools should be done on smaller scales and with efforts to majorly mitigate risks

*we are not near herd immunity and we do not want to move towards natural herd immunity as many people will have to become sick to reach that level; vaccine-based herd immunity is the proper route

*reinfection is possible with COVID-19, but we will have to wait before we know how long immunity is conferred for and what the course of reinfection could look like; with a vaccine, temporary immunity would be augmented by a booster shot

*Warp Speed and ACTIVE are two methods of prioritizing and modifying the operations of research and development for COVID-19

*there is a good chance that a successful vaccine can be scaled up to hundreds of millions of doses by the first quarter of 2021

            Notes from Anthony Fauci

*relative transmission of droplets, aerosols, and contact: I don’t think that there is firm data. There is the assumption that this is droplets, but evidence does not say this is the only path. I would think that a majority of it is the standard droplet (if you stay 6+ feet away, it is less likely the droplet will reach you), but I would not rule out that there is a degree of aerosol, the degree of which I don’t know. Surfaces: we know that the virus will stay on hard enamel, steel, plastic more than corrugated cotton material and things like that. PCR-able versus replication competent survival of the virus on surfaces should be taken into account (it is possible to PCR and detect the virus after it is no longer able to infect and replicate). Relative contribution: if you look at crowds together, you would imagine most of the transmission is droplet rather than surface (fomite). 

*Are people who are PCR-detectable for weeks post infection still actively infectious? What is now evolving into a standard is that if you get a cycle threshold of 35 or more, the chances of the virus being replication competent are miniscule. 

*pre-symptomatic and asymptomatic transmission versus symptomatic transmission: We don’t know the proportions exactly, but if we were to guess we would imagine that the asymptomatic and pre-symptomatic transmission would be substantial. 

*child transmission: children certainly do not get sick as much as adults, but the question is whether they get infected and transmit at high rates. There is a study started recently called the HERO study looking at the rate of infection, transmissibility to family members, and whether they get sick and the antibody response in 6,000 children. Hopefully this will go towards answering the question soon, which has important implications for schools. 

*schools: to address the question of returning to schools, a fundamental principle should be that to the best of your capability given the circumstances you should try to get kids back to school because what we are seeing from downstream, unintended deleterious consequences and ripple effects of children not being in school can be substantial. That said, it varies greatly where you are—we tend to think of the US as a whole, but this may have to be more county by county policies. Counties have to decide either it is not safe to go back to school or, if they decide to open schools, you need to do things that mitigate risk, i.e. alternate day classes, morning-afternoon classes, wearing masks, protecting the vulnerable. There is not one answer to the question, it depends on a number of different circumstances. Paramount, you have to be attentive and sensitive to the welfare and safety of the students and the teachers.

*daily tests and feasibility: something along the line of instantaneous, often taken tests are needed or at least heavily beneficial, particularly in regards to schools, offices, and warehouses. Don’t let the perfect be the enemy of the good—less sensitive tests that catch most high viral load infections that can be taken often are better than less taken more sensitive tests.

*systemic infection by COVID-19 versus pure respiratory: my sense is that the virus is getting out, although we do not have overwhelming proof of this (we may be seeing downstream effects of respiratory infections). We will get more information about this from autopsies, which are currently being looked at in studies.

*fatality rate: this is totally dependent on the number of asymptotic infections. Given just the ballpark, back-of-the-envelope look, it has got to be obviously more than seasonal flu, but its not like SARS (10%) or MERS. With such a large population getting infected, even with a low death rate a lot of people would die. 

*herd immunity: we are currently very far away from herd immunity, if it can be reached. New York is the highest infected population and thats estimated at 22%, which is far too low for herd immunity (around 80% estimated needed). If we want to get herd immunity purely on the basis of infection, excluding vaccine, an awful lot of people will get sick. I am putting my stock into getting the vaccine as soon as possible. 

*immunity and reinfection: when you look at the history of coronaviruses (e.g. the four common cold viruses) the immunity didn’t last that long, maybe six months to a year. We don’t know what length of immunity people would have to this coronavirus, but that is only because we are six months in and this will be shown more with time. If immunity wanes, it is likely you can reinfected. The question becomes if you get reinfected do you have a sub-optimal immunity that then causes enhancement—there is not any evidence yet of people being infected with the traditional common cold coronaviruses getting a worse cold the second time. We have to hope that partial immunity stays and that infections are less severe second time.

*vaccines: if immunity does not last a long time, the question is not whether you should get a vaccine, it will be whether you need a booster shot. If you look at the immune response in a moderate dose, you get a pretty robust neutralizing response, at least for a period of time. Right now we are focusing on that initial immunity, if the immunity wanes then we will focus on that and booster shots later. 

*spike protein: if you theoretically and conceptually look at the protein that blocks the receptor binding to ACE2, it is the traditional place for research and preventative therapeutics to focus on. Focusing on the spike protein works so far. Some vaccines are including other viral proteins in the research and trials.

*viremia: if this is truly a respiratory-borne infection, I would think the immune response would be weaker and would not last long enough. It will be interesting to see if systemic infection confers longer lasting immunity to COVID-19 than a purely respiratory infection. 

*Warp Speed and ACTIVE: ACTIVE is a public-private partnership for prioritization of agents and studies to ensure the resources are accurately and adequately divided among the different priorities. This is more of a think-tank type organization. Operation Warp Speed is an operational group that is looking at diagnostics, therapeutics, and vaccines, primarily therapeutics and vaccines, to actually get involved in the conduct and protocols to harmonize the database, endpoints, and other managerial involvements. ‘Criteria’ is what it looks like in animal studies. ‘Need’ is looking at the places to prioritize, particularly agents that operate early on that prevent a sick person from going to the hospital, e.g. convalescent plasma, hyperimmune globulin, direct antivirals, monoclonal antibodies—all of these have been prioritized and are going into clinical trials. 

*vaccine production and deployment: the horizon is good. We are doing something not at risk to the patient or scientific integrity, but at risk to the money. What happens is the federal government has invested hundreds of millions to billions of dollars into candidates so that companies are not working at risk. This means that if the vaccine does work you have saved many months and if it doesn’t you lose money. Companies are saying that they can produce enough doses for tens to hundreds of millions of doses by the first quarter of 2021 if a vaccine is successful.

*do you see a change in the direction after this pandemic of NIAID so we can have extramural funding for basic science on emerging pathogens that are a little too risky for the normal funding procedure? We had already started doing this before COVID-19, we had a program for prototype pathogens, platform technologies, and pre-selected microbes that we put a fair amount of money in. Now that congress realizes we really have to prepared for the next pandemic or outbreak, we are seeing an infusion of a lot of money into this type of preparedness.

n.b. Dr. Anthony Fauci was on the show in 2013 discussing his history, involvement in the AIDS epidemic, and ending in what kept him up at night, which was the possibility of upcoming pandemics such as COVID-19

By Kiki Warren (