The Index Patient
His name, two years later, is guarded within the privacy of medical files and a family compound of bereaved relatives, his wives, and his children. He was 60 years old. He was a businessman. He lived in Bishah, a small city southeast of the great Saudi port metropolis of Jeddah, and when he became too sick for the Bishah doctors to care for him properly, he was transported to Jeddah, feverish and coughing. There he lay, inside one of the tall white buildings of the Dr. Soliman Fakeeh Hospital, where a diagnostic physician called onto his case happened to be a virology specialist, an Egyptian physician named Ali Mohamed Zaki, who liked to pay close attention to the latest reports of pernicious infectious disease.
All this was at the very beginning, a single week in the middle of June 2012, long before the sick man was understood to be the "index patient."
In clinical reports you don't see the popularized term "patient zero." Once the international detective hunt was under way, as one researcher after another joined in and the search and the connector clues spread around the globe—to Rotterdam and New York City, to the Spanish Canary Islands and Oman and Qatar, to France, England, Greece, Jordan, Egypt, Nigeria, Hong Kong, Malaysia, Australia, Indiana, and, just announced this past week, Florida—and as the questions and implications continue to spread, the man from Bishah has invariably been referred to as the "index patient" or "the patient in Jeddah."
He died in the hospital, 11 days after he was brought in. Zaki says the work on the Bishah man was routine at first, distressing but routine. The patient developed pneumonia, his kidneys began to fail, and Zaki sent sputum samples to the Saudi Ministry of Health, as required by law in such cases, to check for swine flu.
Negative for swine flu. Zaki wondered about hantavirus, which is carried by rodents and can be deadly in humans; when he studied the patient's samples under a microscope he could see the kinds of changes that told him a virus was at work. But no. Negative for hantavirus. Zaki was perplexed, and growing frustrated. He began to guess that the patient had some form of what are called paramyxoviruses—the family that includes measles and mumps. In the 1990s there were scary, lethal eruptions of new paramyxoviruses: in Australia, where the victims were stabled horses and two humans who cared for them up close, and in Malaysia, where a paramyxovirus named Nipah killed more than a hundred people and brought about the slaughter of more than a million pigs.
It didn't seem to be a paramyxovirus, either; Zaki had the lab capabilities to test for that. By the closing days of June 2012 the man from Bishah was deceased, his mourning relatives had come and and gone, and Zaki was not letting go. Maybe his paramyxovirus testing needed another round? As he told me last week, by phone from his current office at the medical school of Ain Shams University in Cairo, "I wanted to know what this is." Some viral malady had felled that patient, something different from anything Zaki could recognize, and apparently something fatal.
So Zaki put some of the samples he had saved from the Bishah man into sterile plastic tubes. He double tubed them for safety, set them inside a metal biohazard box, and shipped the box by courier to Rotterdam, where an institute called the Erasmus MC employs some of the most celebrated virus detectives in the world.
And that was how it started.
The Bat Man
Three months later, and halfway around the planet, a 3 a.m. telephone call in New York City woke a veterinary epidemiologist named Jonathan Epstein. The research organization Epstein works for, EcoHealth Alliance, studies global infection and disease outbreaks, especially those called zoonotic, meaning they are caused by pathogens—malevolent tiny organisms—that have "spilled over," as National Geographic contributing writer David Quammen explained in his recent book about these outbreaks, from nonhuman animals to people. The EcoHealth scientists frequently work alongside a Columbia University team led by molecular biologist and epidemiology professor named Ian Lipkin, whose Center for Infection and Immunity laboratory at Columbia is another world center of pathogen discovery and viral research.
Epstein, to put it unscientifically, is a bat man. Bats were not his initial career specialty, but for many reasons the flying, excreting, fantastically multispecies, globally adaptable bat turns out to be a superior biological starting place for some of the meanest pathogens implicated in zoonotic disease. Epstein and Lipkin had both worked intensely during the international effort to understand and contain SARS, Severe Acute Respiratory Syndrome, which killed nearly 800 people in a global epidemic in 2003. SARS began in China, and for a time it was thought that people were contracting it from the little Chinese animal called the civet. That proved to be wrong: The animal sources of the SARS virus, Epstein and his fellow researchers had figured out, were bats.
The particular family to which the SARS virus belongs has a visually descriptive name: coronaviruses. The "coronas" are knobby rings on each viral particle, which makes the viruses look a bit like crowns; that's what "corona" means in Latin. There's nothing inherently scary about coronaviruses in humans; people pick them up all the time, label them colds, and recover without incident. But SARS-CoV, as it is formally called, was the first coronavirus known to have wrought terrible damage among people it infected. Unlike the common cold, SARS killed a lot of people. It spread easily enough that more than 8,000 individuals were diagnosed with SARS before the 2003 epidemic was brought to a halt, and had it been more contagious, its toll would have been far higher.
And now Lipkin was calling Epstein in the middle of the night because Lipkin had just gotten off the phone with the Saudi Ministry of Health, which was asking for help. Something that looked like SARS-CoV but wasn't—a whole new kind of coronavirus—had been identified in the sputum of the patient from Bishah.
Zaki had suspected as much from a preliminary test he ran himself, and the Rotterdam scientists had confirmed it. Mystery samples arrive at Erasmus every week from all over the world, usually attached to a clinician's plea for enlightenment. Why did this patient die? What is killing these animals? Why don't we understand this? Even so, the lone shipment from Jeddah had stirred enough curiosity at Erasmus to set off a full sequence of lab tests.
The Egyptian doctor was right: It wasn't something familiar. It was a "previously unknown coronavirus," as Zaki and the Rotterdam researchers would call it in their New England Journal of Medicine report and although this new virus did not appear nearly as worrisome as SARS—not yet, anyway—the SARS epidemic had taught the world how crucial it was to move quickly on a warning signal like this.
So it was that Lipkin, Epstein, an EcoHealth disease ecologist named Kevin Olival, and a band of scientists and translators from the Saudi Ministry of Health arrived a few days later at the small airport in Bishah. They came in two waves, Olival following Epstein by a day, each group of foreigners loaded down with odd-shaped luggage: big boxes; massive duffles full of respirators, protective suits, gloves, nets, and syringes; and ten-foot-long cylinder cases carrying a technical device that bears an unfortunate glancing resemblance, as Olival says, to a giant bazooka. Harp traps, these are called. Like much of the apparatus the Americans brought with them, harp traps are used for catching bats.
Was it bats? SARS was carried by bats, and this new virus had many similarities to the one that causes SARS, but at this point the scientists could only speculate. Epstein had stared out the airplane window on the local flight from Riyadh, Saudi Arabia's capital, studying long stretches of desert broken by small patches of green—oases, irrigated crops, date farms. "I'm thinking, What kind of diversity of bats are we going to find in this town?" he told me. Assuming this virus was coming from animals, the "reservoir"—as scientists call the living being that hosts the virus before it makes the jump into humans—could be anywhere.
They'd packed whatever they could think of before they left, including extra-large needles, for example, for drawing blood from livestock. What was the obvious livestock of southwestern Saudi Arabia? "Sheep, goats, cows," Kevin Olival says. "Camels. I remember Jon and I brushing up on how you collect specimens from camels."
Out they all drove, from the Bishah hospital that had welcomed them, past the city shops and restaurants and auto dealers, and on to the residential neighborhood where the patient's survivors lived. There were multiple households to visit—in the Islamically acceptable manner, the late patient had had several wives. All the homes were clean inside, no obvious sign of bats. But bats usually aren't obvious. They hide by day, and it is their nature to secrete themselves in places where humans don't go. The team peered into corners and crevasses, looking for bat feces, which are as tiny as mouse droppings.
No bat trove. "We did a lot of just—ground sleuthing," Epstein says. They learned that the man from Bishah had a business outside town, where there was a warehouse, so they moved the sleuthing farther afield. Palm trees, wells, livestock—the researchers were extracting what they could from whatever livestock they could get to, swabbing and syringing. Some goats. Some sheep. Some camels. And there was this observation, perhaps not significant, but one that stuck in everybody's minds: At home in Bishah, in a paddock beside his family's homes, the index patient—though that was not yet his nickname—kept four camels that had no practical purpose except to live nearby. They were pets.
"The urgency was, this was potentially like SARS again, happening in the Middle East," Jon Epstein says now, which was why he, Olival, and two veterinarians from the Ministry of Health were sitting up late at night outside Bishah, Saudi Arabia, trying to figure out where the bats were coming from. The men could see them, small shadows darting around overhead after dark, but they hadn't been able to find the roosts.
Whatever this virus was, only one person had died of it, as far as anybody knew. By late September 2012 a Qatari man who'd been in Saudi Arabia had turned up sick in London with what was found to be a matching virus; that patient was still alive. But if the virus acted like SARS-CoV, if it was as contagious and perhaps even deadlier, then, as Epstein puts it, "this was a big deal."
That's why he so badly wanted to locate bats. They began driving from one small town to another, inquiring about bats, asking which buildings had been abandoned, until the break finally came: Check on my family's ancestral property, someone said; there are old buildings, built in the traditional dried-mud fashion, long since uninhabited. And in one of those buildings, peering into an underground room into which no human appeared to have ventured for many decades, Epstein saw—just long enough to get excited, before retreating hastily for the respirator and the hazmat suit—a colony, hanging out in the gloom, of some 500 roosting bats.
Now the trapping began. Not lethal trapping; these virus hunters have learned how to get what they need from an animal by annoying it rather than zapping its mortal coil. After five days of weighing, throat swabbing, measuring, pulling bits of wing membrane, and gathering fecal pellets—first within that initial colony and then in others they found later—the group had collected samples from almost a hundred bats, representing seven species. Those samples went straight to New York, where Lipkin and his fellow researchers worked them up—"around the clock, literally day and night," Epstein says.
The virus that killed the man from Bishah still lacked a name. The World Health Organization (WHO), in dispatches that were brisk at first and then began to increase in length and urgency, spent the fall of 2012 calling it "novel coronavirus." In its December dispatch that year, the WHO tabulations mounted; five cases confirmed in Saudi Arabia, two in Qatar, two in Jordan. Both the Jordan patients were confirmed posthumously, from fluid samples kept in storage. They had died in April, before the man from Bishah, during what was described at the time as a brief pneumonia outbreak among some health care workers in Amman.
By the end of May 2013, 44 cases had been diagnosed, half of them fatal. The patients were feverish, hemorrhaging, kidneys failing, unable to breathe. Confirmations of the virus had turned up in England, Germany, and France; all the European patients had, as the WHO notification put it, "direct or indirect connection to the Middle East," which meant, in the case of the French patients, that the first diagnosed man had recently been on vacation in Dubai and that the second diagnosed man had shared the first man's hospital room.
The virus, it seemed, was able to pass from human to human. But why was it showing up now? And where had it started? If it was a zoonotic disease, like SARS—if it originated in bats, like SARS—then were the bats getting directly to the humans, or was there something else in between?
This is where the camels come in.
NGM graphic. SOURCE: ministry of health,
kindom of saudi arabia; world health organization
Another family member, a 47-year-old male died as well. He infected four others, including a 74-year-old female who later died.
The owner exhibited MERS symptoms three days later, and died nine days after that. Five family members became infected; one, a 79-year-old female, died 16 days after the owner’s death.
On August 5, 2013, a sick camel was treated and later sold by its owner, a 38-year-old Saudi Arabian man. Camels are suspected of transmitting the MERS virus to humans.
How one cluster formed