Part I
Chapter 1
Tracking a Mystery
I can still see the words splashed across my computer screen in the early morning hours of January 3. Though we were barely into 2020, I was stuck in an old routine, waking well before dawn and scanning news headlines online. On the BBCâs site, one caught my attention: âChina Pneumonia Outbreak: Mystery Virus Probed in Wuhan.â
Anytime I see a phrase like âmystery virusâ my antennae go up. Anytime that mystery virus is in China, I am even more concerned. Iâve worked my entire life, in one capacity or another, in the fields of immunology, infectious diseases, and public health. My medical specialty is in immunology, and epidemics and pandemics have played a large role in shaping my careerâfrom HIV to avian flu. I was doing work in Asia back in 2002 when the sudden acute respiratory syndrome (SARS) outbreak began. Visceral recollections of the fear that gripped the region and the public health community still haunt me. The numbers of those infected with the virus SARS-CoV-1 werenât extraordinarily high, as pandemics go, but the rate at which it killed those infected was.
Numbers alone donât tell the story of a virus. Every viral outbreak is unique and requires some variation of measures in the handbook to overcome it. When it came to SARS-CoV-1 and China, I recalled the outrage the medical and public health fields felt, and continued to feel. China violated one of the most fundamental principles of managing any infectious disease: to share information early and to share everything you know about a new pathogen. China did neither. With SARS-CoV-1, China may have taken the right actions locally, but it certainly did not do so regionally or globally. Even back then, the world was too small for parochial interests to have outweighed our common interest.
During that outbreak, I sat in coach class on one of my frequent flights to Asia. I had empty row after empty row on which to stretch out and sleep. That I had that choice did more to prevent me from resting well than being crammed shoulder to shoulder would have. Nature abhors a vacuum, and those empty seats were, for me, filled with the specter of the virus and its victims. The flight attendants, airport staff, and the few Asians on my flight all wore masks, adding to the ghostly effect.
The phrase âmystery virusâ goes back even further for me. In the early 1980s, as an active-duty Reserve officer in the U.S. Army while serving as a medical doctor at Walter Reed Army Medical Center, I treated U.S. soldiers suffering from another mysterious illness. Early on, we knew it as adult respiratory distress syndrome (ARDS). As was the case for SARS, we didnât know what was causing patients to die from what started as an atypical respiratory infection. We could see their immune systems were being destroyed, but we still didnât understand why or by what.
We faced a heartrending set of circumstances, seeing previously vibrant, healthy young men being killed by inexplicable, unrelenting immune system deficiencies. With ARDS, too many soldiers died the most terrifying deaths. Their eyes would grow wide as they struggled to breathe. Later, with the soldiers unconscious and medicated to minimize their pain, we could only sit beside them holding their hands and watch as their faces twisted into a rictus of suffering and, despite all our efforts, they essentially drowned in their beds as pneumonia filled their lungs with fluid and starved them of oxygen.
Normally, we could have treated the root cause of the immune deficiency, but for these young men, we had no answers. We saw the evidence of an invasion crippling their bodyâs immune system with one rare infection after another, but we didnât know its cause. We were desperate, and we were humbled. Our patients went from one bad moment to the next. Our interventions were temporary. We lived in a world of so many unknowns but oneâthat these young men were going to die and we couldnât do anything to prevent that.
Returning to the BBC article about this latest âmystery virus,â I noted that the piece focused on two areas: what little was known about the spectrum of the disease (that is, the progression of its symptoms) and how the Chinese citizens and public health officials were responding to it. It was already the annual influenza season in the northern latitudes. If the Chinese had started tracking this outbreak based solely on symptoms and not on a definitive laboratory diagnosis, their initial presumption was that the virus was a seasonal flu variety. That it was now a âmystery virusâ meant it could have been circulating for quite some time already. Were we seeing only the tip of the iceberg?
Using Google Translate, I read Chinese social media entries expressing fear that the new illness could be linked to a SARS outbreak. It was easy to see why some online chatter had made the SARS connection both in China and across Asia. Likely, many of those posting had lived through or lost someone to that earlier SARS and Middle East respiratory syndrome (MERS) crisis. Government officials and citizens across Asia knew both the pervasive fear and the personal response that had worked before to mitigate the loss of life and the economic damage wrought by SARS and MERS. They wore masks. They decreased the frequency and size of social gatherings. Crucially, based on their recent experience, the entire citizenry and local doctors were ringing alarm bells loudly and early. Lives were on the lineâlots of them. They knew what had worked before, and they would do it again.
To that end, my heart sank a bit as I read on. The BBC article reported that Wuhan police had already cracked down on those who were âpublishing or forwarding false information on the Internet without verification.â Would data be withheld again as it was in 2003? Certainly, I recognized the possibility that some of those reporting could be alarmists. But many of them were equally, if not more likely, truth tellers. People risking jail to share information likely meant one thing: the situation was worse than Chinese authorities were reporting.
I hoped this wasnât the case. In the two decades since SARS, officials around the world, including in China, had agreed to focus on global health security and ensure transparency and information sharing early, even when the data points were incomplete. Based on what I was reading, though, the outbreak in China was not just worse than Chinese officials said, but it had likely started earlier. This meant that the virus had already had the opportunity to spread widely before they enacted any measures to contain it. This had implications for the rest of the world.
When it comes to handling emerging pathogens, the Chinese government is not alone in being motivated by self-interest. Economic and reputational concerns lead to a pattern of denial and downplaying. I saw this happen during other outbreaks, ranging from Ebola in West Africa in 2014/16; to the 2014 MERS, which originated in Saudi Arabia; to the latest instance of the Zika virusâs spread in the Americas in 2017. Governments always believe they can contain a virus and prevent it from spreading widely in their country and to others. But viruses can change rapidly, viruses move rapidly across borders, and humans are by nature slow and often too arrogant to act when they should, convinced they have the power to control and contain viruses with technology and win.
THE NEXT FEW DAYS after that first BBC story, my early morning internet-browsing sessions quickly turned into my taking a few moments regularly throughout the dayâsome might say excessivelyâto check where this new virus was and where it was going. Viral outbreaks evolve quickly, so Iâd scour the internet between meetings. Iâd use different search terms. Iâd integrate data points in my head, turning single-source reports into a two-dimensional picture of the new virus on the move.
Much of my career has been shaped by the desire to be of service in the most effective way possible. In college, I chose medicine over my first loves, physical chemistry and math, for precisely this reason. Helping a company like Kodak develop a new and better green dye that didnât turn photo paper yellow over time certainly would have made me money, but it wouldnât have helped change the world.
I switched to medicine when medical research and understanding of our immune system were expanding at an explosive rate. The immune system fascinated me because I saw it as a very sophisticated mathematical equation. It has to strike a very delicate balance and stay within a critical window where it can fight off pathogens while not going too far and destroying the very body itâs meant to defend. That the same system contained both the ability to kill us and to save us enthralled and challenged me.
Throughout my medical/research careerâwhich has taken me from the dawn of broad immunological study to places and organizations like Walter Reed, the National Institutes of Health (NIH), and the CDC; to my role as ambassador-at-large and global AIDS coordinator as part of PEPFAR, at the State Departmentâthe immune system and its role in fighting disease has been at the forefront of my work to mitigate the effects of infectious spread. For many years, this meant the AIDS pandemic, but also other diseases, like tuberculosis.
It has been enormously rewarding work, and I was looking forward to ending my tenure in 2021. I had decided that four decades in public service was a good, round number, and I planned to move on to a second career. I wasnât quite there yet, and had entered into a very busy time with PEPFAR, when I began to read those first accounts coming out of Wuhan, China. I had no special access to other inside information, just a long-held need to keep informed.
Along with monitoring publicly available sources and journalism, I also watched the information coming from the World Health Organizationâs situation reports. As the mystery evolved, I dug deeper, moving beyond mainstream news organizations to new websites and online posts tracking the virus across the globe. Clearly, and as I expected, others saw the need to probe more fully into this developing story. Many in the field of public health began to mobilize, putting together what little data we had to create a more complete picture of what was happening.
On January 6, I read a New York Times story about the same clusters of illnesses the BBC had reported on. It confirmed much of the earlier reporting on them, but also included details about a suspected source. The Huanan Seafood Market in Wuhan had been shut down and decontaminated. The virus that caused SARS and the H7N9 strain of bird flu, which had caused five epidemics of avian flu between 2013 and 2017, had been traced back to similar markets. Close interactions between humans and animals can lead to a virus jumping from one species to another. When animal-to-human transference takes place, and the virus adapts to infect human hosts, we call the resulting virus âzoonotic.â
Novel (new) zoonotic viruses are particularly alarming. All zoonotic viruses are worrying, and the fact that Ebola, SARS, MERS, avian flu, and AIDS were all caused by zoonotic viruses is especially worrisome. (Basically, epidemiology is a field that requires a strong stomach for worrying.) Why? With a zoonotic virus, human beings usually donât have any preexisting immunity to the pathogen that arises in and adapts to a specific animal. The more rapidly it adapts to the human host and can spread from human to human, especially through the air, the more easily the human population can become relatively easy pickings. This is especially true if we are otherwise immunocompromised (as in the case of people who are HIV-positive) or already have other conditions (known as comorbidities) that lessen our ability to produce a fully effective response to pathogens. Airborne pathogens are also particularly dangerous because of the ease with which they are transmitted. As horrific as Ebola and AIDS are, they are not as easily spread, as they are transmitted through the exchange of bodily fluids.
Along with sharing this detail about the market, the Times piece also confirmed two early suspicions I had, both quite troubling. The WHO had received notification from Chinese authorities about a pneumonia-like cluster of infections on December 31, 2019. Yet, by that date, Chinese authorities already had tracking and containment plans in place at airports outside Wuhan to monitor airline passengers arriving from that provincial capital. For the virus to have risen to a level of infection that necessitated these state actions meant it had likely been spreading for weeks, and the Chinese were now aggressively acting to control the spread within their borders while underplaying the outbreak globally. If the virus had in fact been spreading for weeks, it meant the Chinese were also behind in seeing and responding to the outbreak and their containment efforts would fail.
Furthermore, the Chinese were claiming to the WHO that there had been no human-to-human transmission. The only ones infected, they said, had had direct contact with animals at the Huanan wet market. If there was no human-to-human transmission, then the number of victims of the disease would be very small, restricted to those who had been to that single wet market or other wet markets.
Whether the officials in Wuhan or higher up on the chain of command had delayed the release of information by days or weeks was impossible to know at this point. But I did know that any delay could prove deadly. Whatever lessons the Chinese authorities had learned from SARS, they apparently werenât frightening enough to inspire a change to full transparency.
The Times article also confirmed that the Chinese were on the hunt for those who were already exhibiting signs of infection. To complicate matters, China was in winter, a period when many other respiratory viruses circulate, including influenza. It would be hard to tell, therefore, who had pneumonia-like symptoms that were not related to this novel zoonotic virusâat least, not without a test to detect that particular virus. From past experience with other viral outbreaks, I was dubious about this kind of containment strategy.
In tracking viral outbreaks, it is critical to account for four types of spread. The first is asymptomatic, which applies to people who are infected but, despite not having symptoms such as fever, cough, and nasal discharge, are indeed infectious and able to transmit the virus to others. The second is presymptomatic. Immediately following initial infection and replication of the virus and before exhibiting any signs of the infection, these individuals are infectious and will transmit the virus to others during this window. The third, mildly symptomatic, are those with symptoms so mild and non-febrile that they either ignore them or pass them off as symptoms of allergies or a hangover; nevertheless, these individuals are infectious and can transmit the virus to others. The fourth, the fully symptomatic, are those currently presenting typical signs of the infection and able to transmit the virus to others.
Asymptomatic, presymptomatic, and even mildly symptomatic spread are particularly insidious because, with these, many people donât know they are infected. They may not take precautions or may not practice good hygiene, and they donât isolate. As a consequence, they come in contact with more people than someone who is symptomatic. Sick people with high fevers and body aches often canât physically work and tend to stay at home. As a result, those in the first three categories often infect more people than the fully symptomatic do.
Placing a major emphasis on the fully symptomatic is typical of the containment strategies devised to lessen symptomatic spread. Thatâs step one, but if itâs the only step you take, if thatâs the only type of spread you feel you have to mitigate, then containment will never work. In my experience, from the earliest onset of any cluster of infections, you have to be alert to the possibility of, and account for the first three types of spread. In my mind, this is job one.
Sure, there are other variables that determine the scope of an outbreak. Knowing how the virus is spreadâwhether it is airborne or passed on by blood or other body fluidsâthe length of the incubation period after exposure, and how long a person remains infectious to others is also critical information. For example, a person infected with HIV can remain asymptomatic for as many as ten years, which contributes to that virusâs being such a difficult one to control. Some viruses, like the one for measles, are more easily transmitted than others through aerosols (that is, fine particles). Some mutate at a greater rate, becoming more adaptable to their new hostâs changing infectiousness and/or virulence.
However, the one variable that stands out most for me is the type of spread/transmission. After years of experience seeing asymptomatic, presymptomatic, and mildly symptomatic cases being ignored in tabulations, anytime I read a number indicating a confirmed case, I multiply that by a factor of between three and ten. Whatever the number of infected the Chinese had put out, 44 in their first report, I read as between 132 and 440.
The only way to accurately account for all four types of spread is to test as many people as possible early and often. The Chinese werenât doing thisâor, if they were, they were far behind where the outbreak actually was. It seemed highly unlikely that theyâd developed a test specific to this novel virus yet. If they didnât believe (or didnât want to admit) that human-to-human transmission was going on, and if they werenât accounting for asymptomatic spread, then they wouldnât prioritize test development.
Often in pandemics, we focus significant effort on the development of treatments and vaccines, and we neglect the development of tests. This is a fundamental error. In Africa, we had spent years moving from testing only those with AIDS symptoms to testing everyone independent of perceived risk. Weâd saved countless lives through active community testing to determine if individuals had be...