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Special Recap:
Going From A to Z On Coronavirus With Anthony Fauci---A Unique
Interview Conducted By Fellow Scientists
An informative, up-to-date interview with Anthony
Fauci, NIH’s Director of the National Institute of Allergy and
Infectious Diseases and widely regarded as the nation’s go-to expert
on scientific topics related to the COVID-19 pandemic took place in
mid-July on the podcast This Week In Virology. The interview was
remarkable because the virologist- interviewers, Vincent Racaniello
from Mt Sinai School of Medicine and Richard Condit Emeritus
Professor from the University of Florida, have been reporting and
discussing COVID-19 for months and were well prepared and armed with a
full set of key questions on timely and relevant COVID topics. They
peppered him with questions in a collegial manner for 30 minutes. The
session was not without its humorous and candid moments and it is easy
to understand why Fauci has won so many supporters. Below is a recap
of the highlights of the interview.
On Modes of
Transmission
Interviewers wasted no time in asking Fauci about the
relative importance of three routes of transmission often ascribed to
SARS CoV-2, namely droplet spread, aerosol, and contact with
contaminated surfaces. Fauci stated there is no firm data but it is
assumed that droplet spread accounts for most of the transmission. He
noted that without a special event, as happened in the hotel in Hong
Kong with the first SARS virus which traveled vertically and then
across to another hotel, it is impossible to tell that spread is
occurring via aerosol and how much is aerosol.
Fauci added it is “an intelligent guess” that the large
majority of COVID-19 is transmitted by droplet spread within a
distance of 6 feet or less, but that he would not rule out the
possibility that aerosol spread occurs without knowing how much of the
spread is caused that way. Likewise, Fauci said the amount of spread
by direct contact with contaminated surfaces is unclear. It has been
detected on surfaces, but we are unsure if the detected viral material
is really infectious. He allowed that if someone coughed in their
hand, then touched a door knob, and someone else came behind them 15
minutes later, then that could transmit the virus effectively. But in
his view, droplet spread predominates over spread from touching
surfaces.
The question is an important one because it speaks to
the potential effectiveness of wearing masks.
Period of Infectivity
Another important question covered in the interview was
about the length of time a patient is infectious. The question arises
particularly for persons recovering from COVID-19 who remain positive
by polymerase chain reaction (PCR) for extended periods of time. Can
the amount of virus or viral load as measured by “cycle threshold” in
the test be used to evaluate infectiousness because some persistently
positive patients have very low viral loads of 35 or above (the lower
the Ct level the greater the amount of target nucleic acid in the
sample). According to Fauci, the chances that the viral material
detected is infectious or “replication competent” is miniscule and
this threshold value can be interpreted to mean a patient is not
contagious. The Ct values are often not given but are available if
patients ask for them with their test results.
Percent Asymptomatic
or Presymtomatic
Fauci joked that he liked these kinds of questions
because there is no right or wrong answer. He said one can guess at
the answers to such questions provided one does not take the guess too
seriously! He used the outbreak on the Theodore Roosevelt nuclear
aircraft carrier where there was only one or a few symptomatic sailors
out of about 1100 sailors who got infected to establish that there
would have to be a substantial amount of asymptomatic cases in order
to account for this pattern. He could not imagine one person coughing
enough to infect so many others.
Infection in Children
vs Adults
Fauci was asked if children acquire or transmit
infection with COVID-19 differently
than adults
since this question is relevant for what to do about opening schools.
Also, some persons appear to believe that because children do not get
as sick as adults, they can be returned to school safely. Fauci joked
again that this question took them to a “data free zone”.
To correct this lack of information, a new study called
the Human Epidemiology and Response to SARS-CoV-2 (HEROS) will rapidly
enroll 6,000 people from 2,000 U.S. families already participating in
NIH-funded pediatric research studies in 11 cities. The study team
will prospectively follow these children and their families for six
months to determine who gets infected with SARS-CoV-2, whether the
virus is transmitted to other family members, and which family members
with the virus develop COVID-19.
Safest Way to Open
Schools
Fauci believes the fundamental guiding principle should
be that to the best of our capabilities, we should try to get kids
back to school because the unintended deleterious consequences for the
children, their parents, and society can be substantial. Possibilities
will depend a great deal on where children are living. Some counties
may be able to send kids back to school without worrying about
anything, and other places will have enough infection to be unsafe, or
infection levels requiring mitigating risk. Such mitigation activities
could include using alternate day classes, morning or afternoon
classes, wearing masks, and protecting the vulnerable. It is paramount
he added that everyone be attentive to the safety of the children AND
the teachers. Otherwise, schools could reopen and teachers might not
want to come back.
Inexpensive Testing
The interviewers had recently spoken with Michael
Mina at Harvard who is championing the idea of having a
saliva-based antigen test that would only cost a dollar and could be
manufactured in extremely large quantities and made widely available.
Fauci was asked what he thought about that and whether or not it would
ever happen. He said something along those lines is really needed,
essentially an easy test where you can get the answer instantaneously.
It would alleviate a lot of anxiety and it would be important for
public health because you could test a group before sending them in to
class or to a factory knowing that at that given moment--- everyone
was negative.
According to Condit, such tests would be less sensitive
than PCR, but offered that we do not need exquisitely sensitive tests
in these situations if you can catch all the persons with high viral
load who are the contagious ones. It would be enough to identify these
to mitigate the spread of infection. This goes back to the concept
that not all PCR positive patients are infectious. As Fauci noted, the
effort to get highly sensitive tests is a good example of where the
perfect can be considered the enemy of the good!
Local or Systemic Viral Infection
Fauci was asked to what extent he thinks SARS-CoV-2
infection is confined to the respiratory system or whether it escapes
and also infects other organs directly such as the vasculature,
kidneys, and even the brain. Alternatively, should the effects of
COVID-19 being seen in other organs be considered sequelae of the
respiratory infections. Fauci said he believes the “virus is getting
out, although there is not overwhelming evidence that this is in fact
the case. It could be that we are seeing downstream distal effects
that are essentially respiratory. He offered that we will learn the
answer to this question from autopsy studies. If virus is seen in
these other organs, then it will be an open and shut case that this is
a systemic infection.
Infection Fatality
Rate
Another favorite topic of inquiry for epidemiologists
was pursued by the virologist-interviewers who wanted to elicit
Fauci’s best guess about the infection fatality rate.
He reported that his early thinking was the IFR at 1%.
Just giving it a ballpark look, it is obviously more than seasonal
flu, and looking at what goes on with other corona viruses such as
Severe Acute Respiratory Syndrome (SARS) which had an IFR of 10% or
Middle East Respiratory Syndrome (MERS) which kills 37%, the IFR for
COVID-19 has to be around 1%. The calculation is difficult to make
accurately because it depends on the number of asymptomatic cases,
said Fauci.
Seroprevalence
Not content to ask only about fatality, the
interviewers pursued Fauci asking---what do you think is the best
estimate of the seroprevalence of COVID-19 antibodies in the United
States? It is going to vary depending on where you are, but New York
is leading the pack at 22%, he said. Overall Fauci’s best estimate is
that seroprevalence is probably a few percentage points, say 3-4%.
This immediately prompted the question of whether or
not herd immunity can actually be achieved without a vaccine. In
Fauci’s opinion, if we want to get herd immunity purely on the basis
of excluding vaccine, an awful lot of people are going to get sick. “I
don’t want to see herd immunity because we had 70% of the people get
infected.” I am putting my stock in getting a vaccine as quickly as
possible, Fauci added.
Immunity
A great deal of uncertainty has surrounded the kind of
immune response produced by COVID-19, how durable it may be, and how
protective against future infection.
Condit posed the question in five parts, namely, what
fraction of infections generate immunity, does it wane, if so, how
fast does that immunity wane, does reinfection actually occur and at
what rate, and what are the consequences of any reinfection that does
occur—is it milder?
Joking about having to answer five questions in one,
Fauci nevertheless took on the challenge and thought he could meet it
because the questions were related. Based on the experience with other
coronaviruses that cause the common cold, Fauci said he thinks 100% of
infected persons get immunity, but we don’t know how long that
immunity lasts because the virus has not been around long enough to
determine the duration of immunity. To get a good view of the
“immunity landscape” would require a year or two of observation to see
what happens.
Of
course it is possible for immunity to wane, according to Fauci, and a
question buried in there is--does the sub-optimal immunity make things
better or worse upon re-exposure. Fauci said he did not think there is
any evidence that waning immunity makes things worse. Looking for
evidence about this, Fauci offered that persons who have had a
coronavirus cold do not appear to get a worse coronavirus cold the
next time, though he was not sure how well this phenomenon has been
looked at.
Vaccine Efficacy
Given the remaining uncertainty about the quality and
quantity of immunity conferred by a COVID-19 infection, the
interviewers were quick to ask whether or not waning immunity has any
impact on the thinking about how a vaccine
might work. According to Fauci,
the answer is no, at least not on how a vaccine might work. It does
influence thinking about whether or not you might need to get boosted.
The data just published in the New England Journal for
the Moderna mRNA vaccine really does look good said Fauci. You don’t
want to put all your marbles on a study population of only 45
subjects, but they got a pretty robust neutralizing antibody response
using the moderate dose (100mg) vaccine against wild type virus. That
response is as high as or higher than what we find in convalescent
serum. So at least for a finite period of time we can get a good
response, said Fauci. How long it lasts we don’t know, he said, and
added I’ll worry about that later because now the first worry is if
you can get protection long enough to cover a season, and if the
immunity wanes, we can worry about a booster shot.
Vaccine
Make Up
Continuing the interview focused on vaccines, the
virologists asked if it is a good idea for vaccine makers to be
focused so centrally on the spike protein as the key antigen on the
viral surface at the expense of all the other viral proteins that
might be important for inducing immunity.
Fauci noted this was a loaded question, presumably
because of all the different vaccine candidates in contention for
becoming the vaccine or vaccines of choice. In Fauci’s view, if you
look at it theoretically and conceptually, the antibody that blocks
virus binding to the receptor on host cells is classically how you
block infection. He said antibodies to the other components are not
unimportant, however, antibody to the spike protein correlates with
animal protection and so it really looks pretty good.
Duration of Immunity
In seeking to better understand the duration of
immunity, Fauci reminded listeners that if COVID-19 is merely a
respiratory infection then you would expect a weaker response and not
long lasting immunity. On the other hand, if persons with multi-system
disease with COVID have a systemic viremia, then you could get “years
worth” rather than “months worth” of durable immunity. And we know
from other viral diseases like measles that a more systemic infection
produces a more lasting immunity. Again, it is from autopsy studies
that researchers will learn to what extent COVID-19 is a local viral
infection with distant sequelae for other organs or a systemic
infection with virus.
Decision Making Around
COVID-19
Asked to explain what the different groups involved
with operation Warp Speed are doing, Fauci described
Accelerating COVID-19 Therapeutic
Interventions and Vaccines (ACTIV) as a public private
partnership of people from different agencies as well as outside
investigators who are brought together to help prioritize which agents
to pursue and to make sure that resources are appropriately divided
among the different priorities. Operation Warp Speed is more of an
operational group looking at diagnostics, therapeutics, and vaccines
but now mostly focused on therapeutics and vaccines. They do not
actually conduct the work but outline the protocols, identify common
primary and secondary endpoints, and provide other types of
standardizing guidance across studies.
Criteria for Vaccine
Selection
Rich Condit asked what are the criteria used in
prioritization. One is what the proposed vaccine or therapeutic looks
like in animal studies, and what is the current need for it in
treating the disease For example,
Fauci noted we have two therapies now that work well for COVID-19 but
what we need now are agents that work earlier on to prevent a sick
person from going to the hospital. So these earlier acting agents are
the ones we want to study such as convalescent plasma, hyperimmune
globulin, direct antivirals, and monoclonal antibodies—all are being
studied based on the deliberations about prioritization, according to
Fauci.
Vaccine Distribution
In addition to worrying about finding an effective
vaccine or vaccines, government officials must also be concerned about
the adequacy of the eventual vaccine supply. Fauci’s assessment of the
situation is as follows. He believes that deployment looks promising
because the federal government has invested hundreds of millions of
dollars per vaccine candidate and we are having the vaccine makers
proceed whether or not they know if the vaccine will be successful.
They are making these vaccines even before they know if they are going
to work. If it does work, you save many months. If it doesn’t work
you’ve lost a lot of money. So the urgency of the situation dictates
that it’s worth investing the money to save a lot of time. The
companies say they will have enough vaccine by the first quarter of
2021 to be able to start distributing tens if not hundreds of millions
of doses.
Unique Response
In closing their interview, Racaniello and Condit
wanted to know if there has ever been anything like this in response
to a new infection. They already suspected the answer and paraphrasing
Fauci he said there’s never been anything like this for sure. I don’t
like the name Warp Speed because it makes it look like we are
callously rushing out to do things he said. In the way we’ve done
things right now, it is truly remarkable in the view of someone like
me who has been doing this for 40 years and I’ve been involved in the
development of a bunch of vaccines. The speed we have been moving at
is mind boggling and is orders of magnitude more quickly than what we
were doing a decade ago.
Future Funding
In closing, Racaniello wanted to know if Fauci foresees
extra funding being made available for basic science on emerging
pathogens that are a little bit too risky for the normal funding
procedure.
Fauci noted that monies have been available even before
COVID-19 for preparedness work. He said he believes that Congress
realizes that we really have to be prepared for the next one and he is
hoping for the infusion of a lot of money into this type of
preparedness research.
To listen to the 30 minute podcast, readers should
visit This Week in Virology at:
https://bit.ly/32DrG5V ■
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