Planning & Policy Making In An Era Of Uncertainty
By Suresh Kumar
(Figures as of May 20, 2020)
The world could not imagine a pathogen packing such a punch. By May 20, COVID-19 had infected 5.1 million people and claimed over 330,000 lives, 95,000 of them in the U.S. Scientists had long cautioned against the risk of airborne respiratory disease transmitted person to person. Politicians were derelict in providing for it, and the public could not see it. COVID-19 may be just one ten-millionth of an inch or 20 to 400 nanometers in diameter, but it is now visible to all and holding the world hostage. This column responds to requests for providing easy understanding of the viral challenge, how we got here, and the way out.
THE CULPRIT, THE ENTRAPPED, AND A CHAIN OF DEPENDENCE
The pathogen causing COVID-19 is inert, powerless, and dependent on warm-blooded human or animal hosts for survival. Upon invading the host, it feeds and breeds incessantly in relentless pursuit of control to unleash fury on man and civilization.
Human hosts depend on their bodies to produce antibodies to fight the COVID-19 infection. For this, the body must recognize an intruder it has never confronted before and unleash streams of antibodies across millions of cells to annihilate the pathogen. The strength of an individual's immune system determines vulnerability.
Mechanisms of transmission are understood by capturing and isolating species of suspected mammals to determine where the pathogen originated and how it jumps to humans and then from person to person (e.g., by sharing air contaminated with droplets from infected breath).
The goal of public health is immediate inhibition of transmission and eventual extermination of the pathogen.
REMAINING A STEP AHEAD
Pathogens will not go away. They morph and mutate and learn new tricks to resurface with genetic variations that are resistant to new drugs, therapies, vaccines, and pest-eradication programs. Scientists, when they are a step ahead, can forecast and quickly detect outbreaks and have therapeutic building blocks for combating new or known disease, including drug-resistant strains.
Genetic science and decoding the human genome allowed "seeing and codifying DNA and RNA" to tackle viral infections. Yet COVID-19 reminds us every day that we are still learning and that we have more questions than answers. Our zeal to rid the world of disease through aggressive use of new treatments spawned iatrogenic pathogens — those created by medical and other treatments. Now scientists and regulators must accelerate human trials for safety and efficacy of a COVID-19 vaccine and drug candidates while guarding against iatrogenic consequences. Evidence and data drive speed to market for safe and effective new therapies, testing, and treatment. Politicians must set the conditions for success — goals, realistic budgets, and timelines to achieve them — and let scientists and regulators do their jobs. Unfettered public health programs protect populations and prevent illness. Overcoming their "this-too-shall-pass" mentality will allow politicians to see public health programs as investments that defend lives more cost effectively than catastrophic spending to ward off disease outbreaks, which require supplemental economic stimuli to resurrect devastated economies.
Political vacillations delayed testing, contact tracing, and developing therapeutic defenses. Coercing the nation's scientific institutions to rush tests to market compromised the reliability of results for infection and antibodies. The U.S.'s 43 tests per thousand population lags behind that of several countries, and a shortage of supplies and reagents has impaired our knowledge of COVID-19, its transmission, and progression. America cannot afford similar management failures in the development of vaccines and drugs.
THE ROAD TO A VACCINE AND IMMUNITY
Balancing epidemiological risk and economic trade-off is a necessity until the needed vaccines and proven drugs become available. This requires adjusting cultural norms and modifying behaviors beyond frequent hand washing, social distancing, and wearing masks. Substituting a handshake with another form of greeting, banning the consumption of exotic meats and insects, limiting religious congregations, improving how we care for and house the elderly, and developing alternatives to burial customs known to cause hemorrhagic fever and Ebola infections may not appear macho but will save lives.
There are no shortcuts on the road to herd immunity. How contagious a disease is and its reproduction rate determine the percentage of population to be inoculated: Measles requires 90-95 percent, SARS 50-80 percent, and COVID-19 likely 75 percent of the world's population to be vaccinated for realizing herd immunity. This translates to the need of over 6 billion doses for a single-dose vaccine, and many more if boosters are required. Questions abound: What is the pattern and frequency of COVID-19 mutation? How will this impact vaccine efficacy? How long will immunity last? How will access to vaccines be prioritized? How will compliance with inoculation be enforced? How much will the vaccine cost? Who will pay for it? Should price be pegged to the robustness of a country's inoculation program? Who owns the patents?
The fastest vaccine developed was for mumps and took four years. One for HIV has been in development for over 40 years and will likely require 10 more. No vaccine is 100 percent effective, not all produce immunity, and some unintended consequences result in vaccines that make it easier to catch the infection or worsen the disease. (Speeding vaccine development without compromising patient safety requires compressing and even concurrently running clinical study phases.)
Expecting a COVID-19 vaccine by year's end is unrealistic. Getting one by the end of 2021 is aspirational. Approximately 115 COVID-19 vaccine candidates in development is a cause to celebrate and makes one becoming available in 2022 a possibility. "Operation Warp Speed" requires investments now in expensive custom manufacturing facilities with low repurposing potential. It requires expedient investments in vial supplies, cold chains, and storage and distribution facilities before product safety and efficacy are established.
Companies experienced in vaccines leveraging past SARS and MERS research provide confidence, as do the many collaborations already underway targeting a solution to the COVID-19 crisis. The prospect of human mRNA vaccine codifying messenger RNA to stimulate the body to produce its own antigens is exciting, as it could exponentially reduce manufacturing time and cost. The technology, though, is untested; it needs ensuring that mRNA is stable and proving that it will not break down in the body.
BIOETHICS AND TRANSPARENT COMMUNICATIONS INSPIRE PUBLIC TRUST
Government investments in commercial vaccine and manufacturing ventures are a template for future health security. The public has the right to know what the investment must yield and when the funds will be deployed. It also needs to know the principles regarding who the drug will be made available to.
In times of public health and national crisis, political speak and marketing hype diminish corporate and government credibility and destroy public trust. Rapidly sharing patient safety study results and adverse events can save lives. Conversely, press releases with few details can raise false expectations, spook the public and financial markets, and risk tarnishing a company's reputation. We are all entitled to "straight talk" — detailed and defensible retrospective milestone achievements and the prospective time to market for a vaccine or drug. Authenticity and facts trump anecdotes; "some" is not a number, and "soon" is not a time frame.
Preparing for the future, let alone predicting it, is never an exact science. It requires an informed, considered judgment and a predictable process. Enacting policy while addressing human suffering during a pandemic begins with acknowledging what we know and what we don't. Then, it involves accepting the risks worth taking and reporting transparently on the realistic plans being pursued. Not knowing everything up front has rarely impaired our judgment or our pursuits to improve lives.
SURESH KUMAR serves on the board of Jubilant Pharmaceuticals and Medocity. Formerly, he was U.S. Assistant Secretary of Commerce and executive VP at Sanofi.