If longevity is the goal, then we must advocate for effective biodefense to deal with
novel pandemics or face death from that quarter. For SARS-CoV-2, lack of early symptoms
in all cases, and lack of any symptoms in approximately half, makes control of super-spreaders
1
by contact tracing and quarantine impractical. Thus, social distancing, masking, and
mass lockdown was created to prevent overwhelming the medical system. That worked,
but with economic impact that could kill millions or cast them into dire poverty.
2,3
Economic disruption also spreads like a virus, but one that is impossible to “socially
distance” from. Follow-on effects from the loss of income in these sectors will exacerbate
these direct declines. In the developed world, after panic buying, people hoard money,
causing the turnover of money to drop, thus reducing the effective money supply.
4
The lockdown dramatically cuts both demand and supply: the weekly increase in new
unemployment claims for March 28, 2020 was 6.6 million, versus a recent average of
210,000.
5
This is eight times the largest percentage rate of increase in unemployment during
the Great Depression. The World Trade Organization (WTO) estimates greater impact
than the 2008 Global Financial Crisis,
6
and historically underestimates.
Conservative counting of industries directly affected—education, entertainment, accommodation,
restaurants, real estate, and passenger transportation—represents 24% of U.S. GDP,
almost equal to the total fall in GDP between late 1929 and 1933 (the bottom of the
Great Depression) of 26%. Follow-on effects from the loss of income in these sectors
will exacerbate these direct declines. A financial crisis will follow, since private
debt to GDP levels is three times the level at the time of the Spanish flu.
7
Without strong government action, a financial pandemic will follow the medical pandemic.
Figure 1 shows the missing global economy from 2008's crisis is $8.074 trillion for
2019. For the United States, relative losses averaging $1.8 trillion per year comprise
12 × $1.8 trillion GDP years, or ∼$21.6 trillion cumulatively. This is what a 4.2%
GDP maximum loss caused.
FIG. 1.
Upper: GDP% loss by year
. Example projection estimates show where Greece and the United States should be relative
to actual GDP. Respective 2019 GDP deficits: Greece 42.0% and United States 7.8%.
Shading emphasizes deficit regions for Greece (brown) and United States (blue), showing
time impact. Netherlands removed for readability.
Lower: 2019 GDP deficit due to 2008 crisis, based on 2000 starting point fit
. Total 2019 GDP deficit is $8.074 trillion. WTO expects worse effect than 2008.
4
Source: BIS tables.
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GDP, gross domestic product; WTO, World Trade Organization.
There is a general economic principle to keep in mind. Destruction is quick. Rebuilding
is not.
It should be clear we need better methods than lockdown quarantine to combat pandemics
such as SARS-CoV-2.
Fifteen years ago the first author was one of several to urge U.S. Congress to adopt
a biodefense strategy
8
updated here as three tiers:
(1)
Recognize that medicine is biodefense. If a genuine bioweapon release occurs, it is
virtually certain to be a nonstate actor, and that event could make SARS-CoV-2 a relative
tea party. Mortality rates in the 60%–90% range are possible. This means that a national
health care system is a fundamental security requirement so that nobody gets missed,
because infectious diseases circulate well in poor and illegal populations.
(2)
We need to continuously monitor circulating viruses through excess blood/serum, and
to inventory zoonotic viruses in wild animals. The former requires changing privacy
laws in some nations to enable monitoring for public health purposes. Both require
active prospecting for new microorganisms by sophisticated methods.
(3)
We need to set up and regularly exercise facilities for producing and deploying crisis
vaccines rapidly in three waves: rolling out nucleotide vaccines expressing whole
capsid/envelope proteins, then protein component/killed vaccine with adjuvant, followed
by live attenuated/engineered vaccine. Each type has strengths. Nucleotide vaccine
is quick to design and produce, safe for the immune compromised, and tends to avoid
Th2 issues, but DNA is expensive to scale, whereas RNA is not. Component/killed vaccine
often scales well and is also safe for the immune compromised. Live vaccine likewise
scales well, although there are exceptions, and it usually produces the most robust
immunity.
This vaccine strategy needs a special regulatory framework that eliminates roadblocks.
Vaccines are very safe, and they work reliably on virtually all viruses when put together
in straightforward ways. Rare exceptions like HIV are just that—incredibly rare exceptions.
There are some risks, but reactions usually resolve.
9
The smallpox vaccine had a 1 in 175 risk of myopericarditis.
10
The attenuated polio vaccine still has reversion. These vaccines are evaluated correctly
based on relative risk, which includes mortality, morbidity, plus economic harm, and
national security.
The purpose of a public health system vaccine crisis capability should be the immediate
release and production of vaccines, in a wartime-like operation. Done this way, vaccines
could be available weeks or a few months after the initial identification of the pathogen.
Rollout becomes the trial, with monitoring evaluated strictly on risk versus benefit,
that includes economic impact (which is the poverty and death impact of inaction versus
action) as well as a casualty ratio.
Risk–benefit analysis in vaccines has examples that are far off base today. A respiratory
syncytial virus vaccine in 1956 that caused some children <2 years to have risk of
a worse respiratory illness. This vaccine was pulled, and yet it was fine for those
>2 years.
RotaShield was a Wyeth vaccine in 2000 that had five cases of intussusception, causing
it to be pulled. Intussusception is easily treated, and this was likely a fluke not
related to the vaccine itself; but even if it was a rare side effect, the sensible
thing to do was keep it until a replacement appeared. Rotavirus killed more than half
a million children a year. From this decision, in the intervening years before a new
vaccine arrived, >4 million children had no chance of survival, including 320 in the
United States and 1800 in Europe.
During the 2014 Ebola epidemic, several vaccines had been in development for a decade.
Although two trials occurred, by withholding these vaccines instead of an immediate
rollout, 28,852 people died and African nations incurred severe economic damage, including
complete collapse of the Liberian medical system 6 months after the epidemic started.
In 2018's Ebola outbreak, not until August was a vaccine introduced
11
; containment stopped it at 3000 odd deaths.
Foot dragging and wild misjudgment of vaccine risk are not acceptable. Likewise, withholding
vaccines because of bureaucracy when a pandemic is raging. Since roadblocks are not
just governmental, but also from corporate liability avoidance, legislation needs
to include the ability for public health authorities to order production and release
until something better is available, and to shield developers against liability.
Vaccines are the safest form of medicine we have, and the most cost-effective. For
comparison, NSAIDS kill tens of thousands worldwide each year, and an estimated 7600
in the United States alone. Orthopedic surgery has an acute mortality rate of 1%.
Total mortality from adverse reactions to vaccines in the past 50 years is very low,
in the range of hundreds, and even these were mostly avoidable. Contamination and
quality control are the major concerns in the modern world. We are long past the ignorance
that led to the reversion problems of the original Salk vaccine.
For this pandemic, open the gates and release the vaccines (#ReleaseTheVacc). Nucleotide
vaccines are ready. They should have virtually zero safety issues. These will be protective
against serious disease and prevent death in most cases, although not sterilizing.
However, very few vaccines produce truly sterilizing immunity. The extremely rapid
scaling of RNA vaccine makes it the superior method for mass deployment. RNA vaccines
also have better antibody response than DNA vaccines.
Component and killed vaccines are also safe for immune compromised. Release them now
as well.
Live recombinant and attenuated vaccines need the most testing, but even those can
be moved through much faster. One can examine the design, looking at the base virus
used and see safety of the scaffold in humans. Similarly, for attenuated vaccines,
we can look at the gene(s) selected for removal/modification to attenuate the virus.
Unlike Salk's era, we can do rational design because we understand the genes of viruses
now.
Nothing is absolutely zero risk. But risk must be weighed against certainty of doing
nothing, which here and now is too extreme.
We also recommend a backstop based on vaccinia (or some other suitable virus) for
expression of novel virus proteins. Vaccinia can be quickly engineered to express
virtually anything. As a live vaccine, in a dire emergency, such an engineered vaccine
could be administered with directions to take a scraping from the sores that develop,
and scratch it onto the shoulders of as many people who are not immune compromised
as possible. This is the fastest possible rollout of a biodefense vaccine, although
it comes with significant risk. The first author did scenarios for biodefense, and
there are situations wherein this kind of rollout is the only plausible method to
save a nation from collapse.
We call for all elements of this program to be legislated and supported by governments
around the world. We suggest that it be supported by international treaty, with sanctions
against nations that fail to comply. When nations are at risk of serious economic
disruption or overwhelming health care facilities, there is no justification for current
policies that leave no alternative but mass death and severe economic damage. It is
worth remembering that the last global depression was ended by world war and a new
world order.