Northwest Arkansas Democrat-Gazette

PROFILE OF A KILLER

Unraveling the deadly new coronaviru­s

- ADAM GELLER AND MALCOLM RITTER

“There’s light at the end of tunnel, but it’s a very, very long tunnel. There’s a lot we don’t know. But I think it’s absolutely certain we’re going to be adapting to a new way of life. That’s the reality.”

— Dr. Irwin Redlener, director of the National Center for Disaster Preparedne­ss at Columbia University

NEW YORK — What is this enemy? Seven months after the first patients were hospitaliz­ed in China battling an infection doctors had never seen before, the world’s scientists and citizens have reached an unsettling crossroads.

Countless hours of treatment and research, trial and error now make it possible to take much closer measure of the new coronaviru­s and the lethal disease it has unleashed. But to take advantage of that intelligen­ce, we must confront our persistent vulnerabil­ity: The virus leaves no choice.

“It’s like we’re in a battle with something that we can’t see, that we don’t know, and we don’t know where it’s coming from,” said Vivian Castro, a nurse supervisor at St. Joseph’s Medical Center in Yonkers, just north of New York City, which struggled with its caseload this spring.

Castro had treated scores of infected patients before she, too, was hospitaliz­ed for the virus in April, then spent two weeks in home quarantine. As soon as she returned to the emergency room for her first shift, she rushed to comfort yet another casualty — a man swallowing the few words he could muster between gasps for air.

“It just came back, that fear,” she said. “I just wanted to tell him not to give up.”

The coronaviru­s is invisible, but seemingly everywhere. It requires close contact to spread, but it has reached around the globe faster than any pandemic in history.

Covid-19 was not even on the world’s radar in November. But it has caused economic upheaval echoing the Great Depression, while claiming more than 580,000 lives. In the U.S. alone, the virus has already killed more Americans than died fighting in World War I.

Even those figures don’t capture the pandemic’s full sweep. Nine of every 10 students worldwide shut out of their schools at one point. More than 7 million flights grounded. Countless moments of celebratio­n and sorrow — weddings and graduation­s, baby showers and funerals — put off, reconfigur­ed or abandoned because of worries about safety.

In short, the coronaviru­s has rescripted nearly every moment of daily life. And fighting it — whether by searching for a vaccine or seeking to protect family — takes knowing the enemy. It’s the essential first step in what could be an extended quest for some version of normalcy.

“There’s light at the end of tunnel, but it’s a very, very long tunnel,” said Dr. Irwin Redlener, director of the National Center for Disaster Preparedne­ss at Columbia University.

“There’s a lot we don’t know. But I think it’s absolutely certain we’re going to be adapting to a new way of life. That’s the reality.”

★★★

The new coronaviru­s is roughly 1,000 times narrower than a human hair. But scrutinize­d through an electron scope, it is clear this enemy is well-armed.

Coronaviru­ses, including the newest one, are named for the spikes that cover their outer surface like a crown, or corona in Latin. Using those club-shaped spikes, the virus latches on to the outer wall of a human cell, invades it and replicates, creating viruses to hijack more cells.

Find a way to block or bind the spikes and you can stop the virus.

Once inside a human cell, the virus’ RNA, or genetic code, commandeer­s its machinery, providing instructio­ns to make thousands of virus copies.

But the coronaviru­s has a weakness: an outer membrane that can be destroyed by ordinary soap. That neutralize­s the virus, which is why health experts emphasize the need to wash hands.

Like organisms, viruses evolve, searching for traits that will ensure survival, said Charles Marshall, a professor of paleontolo­gy at the University of California and self-described “deep time evolutiona­ry biologist.”

“Coronaviru­ses fit into the standard evolutiona­ry paradigm extremely well, which is if you’ve had some innovation, you get into some new environmen­t … you get into a human and you do well, you’re going to proliferat­e,” Marshall said.

There are hundreds of coronaviru­ses, but just seven known to infect people. Four are responsibl­e for some common colds. But in 2002, a virus called SARS, for severe acute respirator­y syndrome, spread from China to sicken about 8,000 people worldwide, killing more than 700. Another coronaviru­s called Middle Eastern respirator­y syndrome, or MERS — identified in 2012 — spread to humans through camels.

The new coronaviru­s, though, has captivated scientists’ attention unlike any in decades.

When researcher Thomas Friedrich logged on to his computer at the University of Wisconsin-Madison after a meeting in January, he found colleagues had been franticall­y posting messages to one another about the new virus.

“People were getting increasing­ly excited and beginning to brainstorm ideas,” said Friedrich, who has spent years studying other infectious diseases.

Now much of Friedrich’s lab is focused on the coronaviru­s, studying its spread in Wisconsin, and collaborat­ing with scientists around the world examining the disease’s behavior in monkeys.

Even early on it was clear this virus posed a major threat, he said. Human immune systems had never encountere­d it. And unlike Zika, whose spread can be controlled by targeting mosquitoes, or AIDS, which most often requires sexual contact, the new virus is readily transmitte­d through droplets in the air.

“It had all the hallmarks, to me, of a potential pandemic,” Friedrich said. “Basically, everyone in the world is susceptibl­e.”

★★★

The new virus has breached borders and claimed victims with stealth and speed that make it difficult to track.

Scientists are fairly certain the disease originated in bats, which harbor many coronaviru­ses. To get to humans, it may

have been passed through another animal, possibly consumed for meat. By late January, when Chinese authoritie­s walled off the city of Wuhan, where the disease was first diagnosed, it was too late to stop the spread.

The most severe pandemic in recent history, the “Spanish flu” of 1918, was spread by infected soldiers dispatched to fight World War I. But aboard ships, it took weeks for the troops and the disease to cross oceans.

Now, with more than 100,000 commercial flights a day ferrying tourists, business travelers and students around the globe, the new virus spread rapidly and virtually invisibly, said medical historian Mark Honigsbaum, author of “The Pandemic Century: One Hundred Years of Panic, Hysteria and Hubris.”

“By the time we woke up to the outbreak in Italy, it had been there for weeks if not months,” he said.

Soon after the first case in Wuhan, Chinese tourists with the virus traveled to France. But doctors there reported recently a fishmonger contracted the disease even earlier than that, from an unknown source. On January 21, the first confirmed U.S. case was reported in Washington, in a man who had traveled to Asia.

“It’s one person coming in from China and we have it under control. It’s going to be just fine,” President Donald Trump said at the time. Ten days later, he blocked entry to most travelers from China.

But genetic analysis of samples taken from New York patients showed most of the virus present arrived from Europe instead, and took root in February — well before anyone thought about quarantini­ng after a trip to Madrid, London or Paris.

★★★

Since February, when Dr. Daniel Griffin began treating patients suspected of having covid-19, he’s cared for more than 1,000 people with the disease, first noted for attacking the lungs. But the infection certainly doesn’t stop there.

“I am actually shocked,” said Griffin, a specialist in infectious diseases at New York’s Columbia University Medical Center. “This virus seems to leave nothing untouched.”

Scientists are getting a handle on the many ways the disease affects the body, but it’s a scramble.

The lungs are, indeed, ground zero. Many patients find themselves gasping for breath, unable to say more than a word or two.

Even after five days in the hospital, Vivian Castro, the nurse who became infected, said she returned home struggling for air.

“I climbed two flights of stairs to my room and I felt like I was going to die,” she said.

The reason why becomes clear in autopsies of those who have died, some with lungs that weigh far more than usual. Under a microscope, evidence of the virus’ destructio­n is even more striking.

When Dr. Sanjay Mukhopadhy­ay examined autopsy samples from a 77-year-old Oklahoma man, he noted changes to the microscopi­c sacs in the patient’s lungs. In a healthy lung, oxygen passes through the thin walls of those sacs into the bloodstrea­m. But in the Oklahoma patient, the virus had turned the sac walls so thick with debris that oxygen was blocked.

The thickened walls “were everywhere,” preventing the lungs from sustaining the rest of the body, said Mukhopadhy­ay, of Ohio’s Cleveland Clinic.

Autopsies reveal “what the virus is actually doing” inside patient’s bodies, said Dr. Desiree Marshall, a pathologis­t at the University of Washington who recently examined the heart of a Seattle man who died from disease.

“Each autopsy has the chance to tell us something new,” she said. And those insights from the bodies of the dead could lead to more effective treatment of the living.

The coronaviru­s, though, keeps raising fresh questions. It left the hearts of two men in their 40s, recently treated by Griffin, flaccid and unable to pump enough blood. Some younger people have arrived in emergency rooms suffering strokes caused by blood clotting, another calling card.

Kidneys and livers fail in some patients and blood clots put limbs at risk of amputation. Some patients hallucinat­e or have trouble maintainin­g balance. Some get a treatable paralysis in arms or legs. Many have diarrhea, but often don’t mention it until Griffin asks.

Their explanatio­n? “That’s the least of my problems when I can’t breathe.”

Initially, doctors often put patients on ventilator­s if their blood oxygen levels dropped. But death rates were so high they now try other strategies first, like turning patients on their stomachs, which can help them breathe. The truth is that hospital workers are learning as they go, sometimes painfully.

“Every patient that I see, I think that could’ve been me,” said Dr. Stuart Moser, a cardiologi­st hospitaliz­ed in New York in March after he was infected. He recalls fearing that he might be put on a ventilator and wondering if he’d ever see his family again. Now, back at work, he said much of what he and his colleagues have learned about the virus’ myriad effects enables them only to treat patients’ symptoms.

“It’s difficult because they have so many problems and there are so many patients,” Moser said, “and you just want to do the right thing — give people the best chance to get better.”

★★★

In recent weeks, researcher­s have recruited 3,000 patients from around the world in a bid to solve a puzzling anomaly. Why does the coronaviru­s ravage some previously healthy patients, while leaving others relatively unscathed?

The project, called the covid Human Genetic Effort, focuses on each person’s unique genetic makeup to seek explanatio­ns for why some got sick while others stay healthy. It’s one of several projects looking for genetic causes of susceptibi­lity, including recent work by other labs suggesting a link between blood type and risk of serious illness.

“Step one is understand­ing and step two is fixing. There is no other way,” said one of the project’s leaders, Jean-Laurent Casanova, of The Rockefelle­r University in New York. He is paid by the Howard Hughes Medical Institute, which also helps fund The Associated Press Health and Science Department.

His project focuses on people 50 or younger who had no health problems before the coronaviru­s put them in intensive care. But the question of why the disease affects people so differentl­y has broader implicatio­ns.

It’s not clear, for example, why the disease has had such a limited impact on children, compared to other age groups. People older than 65 are well over 100 times more likely to be hospitaliz­ed for the virus than people under 18. But so far, there’s no explanatio­n why.

Do children resist infection for some reason? Or is it that, even when infected, they are less likely to develop symptoms? If so, what does that mean about their chances for passing the infection along to others, like their grandparen­ts?

These aren’t just academic questions. Answers will help in assessing the risks of reopening schools. And they could eventually lead to ways to help make older people resistant to the disease.

In largely sparing children, the pandemic virus echoes the bugs that caused SARS and MERS, said Dr. Sonja Rasmussen, a professor of pediatrics and epidemiolo­gy at the University of Florida.

Scientists wonder if children might have some key difference in their cells, such as fewer of the specialize­d proteins that the coronaviru­s latch onto. Or maybe their immune systems react differentl­y than in adults.

While the virus has mostly bypassed children, researcher­s have recently been troubled by a serious, albeit uncommon, condition in some young patients, that can cause inflammati­on in hearts, kidneys, lungs and other organs. Most patients recovered, but the potential for long-term damage remains uncertain.

“This is what happens with a new virus,” Rasmussen said. “There’s a lot we don’t know about it. We’re on that steep learning curve.”

★★★

With states and countries opening in the face of an ongoing pandemic, it’s even more crucial to find solutions. At least the last few months have spotlighte­d the most critical questions.

Can people who have been infected with the disease get it again?

Dr. Anthony Fauci, the U.S. government’s top infectious disease expert, has said having the disease once should confer some degree of immunity. But it’s not clear how much or for how long, or what levels or types of antibodies people must have to protect them against future illness.

If some people harbor the virus without symptoms, how can we block transmissi­on?

The reality is that many infected people will never feel symptoms or get sick. That means temperatur­e checks and other strategies based on symptoms won’t be enough to stop it. Instead, many experts believe, widespread testing is needed to find silent carriers, isolate them until they are no longer contagious, and track down those they may have infected. Masks and distancing can help prevent infection and slow the spread of the virus.

Will researcher­s find medicines that can be used to treat the disease?

Hundreds of studies are under way, testing existing medicines and experiment­al ones. So far, only one — a common steroid called dexamethas­one — has been shown to increase survival. An antiviral medicine, remdesivir, has been shown to shorten recovery time. Two others — the malaria drugs chloroquin­e and hydroxychl­oroquine — have not proven safe or effective for treating covid-19 in large-scale trials, but some studies are still testing them to see if they might help prevent infection or illness.

How long will it take to find a vaccine?

Scientists in more than 150 labs around the world are pursuing a vaccine and nearly two dozen candidates are in various stages of testing. But there’s no guarantee any will pan out. Finding out if any offer true protection will require testing thousands of people in places where the virus is spreading widely. Some huge studies are expected to begin this month.

“It’s almost the Manhattan Project of today, where an enormous amount of resources are being devoted to this,” said Rene Najera, an epidemiolo­gist at Johns Hopkins University and the editor of a vaccine history website run by The College of Physicians of Philadelph­ia.

In the U.S., the goal is to have 300 million doses of potential vaccines by January. But any that fail tests will have to be thrown out. The World Health Organizati­on has called for equitable sharing of any eventual vaccine between rich and poor countries, but how that will happen is far from clear.

It’s also uncertain how useful any vaccine will be if a sizable number of people, their skepticism fed by misinforma­tion, refuse to be inoculated.

Even an effective vaccine will not address the likelihood that, given the large number of coronaviru­ses and increasing contact between people and the animals harboring them, the world is very likely to face other pandemics, said Honigsbaum, the medical historian.

That means uncertaint­y will linger as a hallmark of the new normal.

The knowledge gained about the coronaviru­s could prove invaluable in defusing that doubt and, eventually, in defeating the enemy. The real uncertaint­y, Redlener said, is whether people will use the lessons learned to protect themselves from the virus — or downplay the threat at their peril.

 ?? (Courtesy Photo/National Institute of Allergy and Infectious Diseases) ?? This 2020 electron microscope image provided by the National Institute of Allergy and Infectious Diseases-Rocky Mountain Laboratori­es shows SARSCoV-2 virus particles, which cause covid-19, isolated from a patient in the U.S., emerging from the surface of cells cultured in a lab.
(Courtesy Photo/National Institute of Allergy and Infectious Diseases) This 2020 electron microscope image provided by the National Institute of Allergy and Infectious Diseases-Rocky Mountain Laboratori­es shows SARSCoV-2 virus particles, which cause covid-19, isolated from a patient in the U.S., emerging from the surface of cells cultured in a lab.
 ?? (AP/Ted S. Warren) ?? Dr. Desiree Marshall prepares samples from the preserved heart of a person who died of covid-19 related complicati­ons, as she works in a negative-pressure laboratory in Seattle. “Each autopsy has the chance to tell us something new,” she says. And those insights from the bodies of the dead could lead to more effective treatment of the living.
(AP/Ted S. Warren) Dr. Desiree Marshall prepares samples from the preserved heart of a person who died of covid-19 related complicati­ons, as she works in a negative-pressure laboratory in Seattle. “Each autopsy has the chance to tell us something new,” she says. And those insights from the bodies of the dead could lead to more effective treatment of the living.
 ?? (AP/Ted S. Warren) ?? Dr. Nicole Yarid, an associate medical examiner for King County in Washington, poses for a photo Tuesday wearing the protective equipment she uses when she does autopsies on people who have died from covid-19 at the Medical Examiner’s office in Seattle.
(AP/Ted S. Warren) Dr. Nicole Yarid, an associate medical examiner for King County in Washington, poses for a photo Tuesday wearing the protective equipment she uses when she does autopsies on people who have died from covid-19 at the Medical Examiner’s office in Seattle.
 ?? (AP/Ted S. Warren) ?? Dr. Desiree Marshall, director of autopsy and after death services for University of Washington Medicine, examines the preserved heart of a person who died of covid-19 as she works in a negative-pressure laboratory in Seattle. Seven months after the first patients were hospitaliz­ed in China battling an infection doctors had never seen before, countless hours of treatment and research are providing a much closer look at the new coronaviru­s and the lethal disease it has unleashed.
(AP/Ted S. Warren) Dr. Desiree Marshall, director of autopsy and after death services for University of Washington Medicine, examines the preserved heart of a person who died of covid-19 as she works in a negative-pressure laboratory in Seattle. Seven months after the first patients were hospitaliz­ed in China battling an infection doctors had never seen before, countless hours of treatment and research are providing a much closer look at the new coronaviru­s and the lethal disease it has unleashed.
 ?? (Chinatopix via AP) ?? Shi Zhengli works Feb. 23, 2017, with other researcher­s in a lab at the Wuhan Institute of Virology in Wuhan in central China’s Hubei province. On Dec. 30, 2019, Shi, famous for having traced the SARS virus to a bat cave, was alerted to the new disease, according to an interview with Scientific American. By late January, when Chinese authoritie­s walled off Wuhan, where the disease was first diagnosed, it was too late to stop the spread.
(Chinatopix via AP) Shi Zhengli works Feb. 23, 2017, with other researcher­s in a lab at the Wuhan Institute of Virology in Wuhan in central China’s Hubei province. On Dec. 30, 2019, Shi, famous for having traced the SARS virus to a bat cave, was alerted to the new disease, according to an interview with Scientific American. By late January, when Chinese authoritie­s walled off Wuhan, where the disease was first diagnosed, it was too late to stop the spread.
 ?? (AP/Ted S. Warren) ?? Dr. Nicole Yarid, an associate medical examiner for King County in Washington, puts on a gown Tuesday as she demonstrat­es the protective equipment she uses to do autopsies on people who have died from covid-19 related complicati­ons at the Medical Examiner’s office in Seattle.
(AP/Ted S. Warren) Dr. Nicole Yarid, an associate medical examiner for King County in Washington, puts on a gown Tuesday as she demonstrat­es the protective equipment she uses to do autopsies on people who have died from covid-19 related complicati­ons at the Medical Examiner’s office in Seattle.
 ??  ?? This 2020 electron microscope image made available by the National Institute of Allergy and Infectious Diseases shows a novel coronaviru­s SARS-CoV-2 particle isolated from a patient, in a laboratory in Fort Detrick, Md. (Courtesy Photo/National Institute of Allergy and Infectious Diseases)
This 2020 electron microscope image made available by the National Institute of Allergy and Infectious Diseases shows a novel coronaviru­s SARS-CoV-2 particle isolated from a patient, in a laboratory in Fort Detrick, Md. (Courtesy Photo/National Institute of Allergy and Infectious Diseases)

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