A week after testing positive for Covid-19, Joshua Fiske drove himself to a New Jersey hospital with a fever nearing 104 and a blood oxygen level extraordinarily low for an athletic 47-year-old. An X-ray revealed pneumonia in both lungs.
He was admitted but his condition worsened: He felt cold enough to shiver under five blankets in one moment, then sweated through his hospital gown the next. He worried he wouldn’t pull through. He called his wife to say he loved her. He called his two sons and asked them to take care of their mother, then tapped out a letter to them on his phone. He wanted them to grow into good, kind men, he told them. Above all, he urged, “Don’t let this event define you.”
Among the many mysteries of Covid-19 is why relatively healthy young people suddenly become critically ill — or die.
One answer is what was happening to Fiske. His body had begun to fight the coronavirus with the immune system’s equivalent of thermonuclear weapons — proteins so powerful they risk annihilating the body they are supposed to protect. This massive over-reaction, known as a cytokine storm, is believed to be a major reason that a growing number of exceedingly fit people find themselves fighting for their lives.
Immune cells release cytokines as part of the normal response to infections, but in many Covid-19 patients, this process gets out of hand, leading to inflammation and fluid buildup in the lungs. The storms pose a dilemma for doctors: Prescribe medications that tamp down the immune system at the wrong moment, and the body will be defenseless against the coronavirus or any opportunistic infection that’s taken root. Do nothing, and there’s a good chance the massive attack will shut down the lungs and other vital organs.
Scientists have begun to study how many patients who become critically ill with Covid-19 experience these storms, which were initially seen in some of the earliest patients hospitalized in Wuhan, China. In one study of 53 patients in China, researchers concluded that three particular cytokines were correlated with disease severity and death. (The paper was posted on a preprint server and hasn’t been peer-reviewed.)
The crucial question of what portion of critically ill patients are vulnerable to cytokine storms — and why — awaits more detailed research, said Randy Cron, a rheumatologist at the Children’s Hospital of Alabama and the University of Alabama at Birmingham. “We don’t know the numbers, but among previously healthy people ages 20 to 60 who require hospitalization, a significant number are suffering from cytokine storms in addition to the virus,” Cron told STAT.
There are not yet data for the number of patients with cytokine storms who require ICU or ventilator care, Cron said. “But outside the 85-year-old with hypertension or diabetes, if you are that sick, it’s very likely that that’s what you are experiencing,” he said.
Fiske was among the last people anybody would have expected to become seriously ill. A Livingston, N.J., urologist, he took up running seven years ago at the age of 40. Since then, he has completed the New York City marathon, and six half marathons from Philadelphia to Brooklyn, and he was running 16 to 20 miles a week.
On March 16, after a day in the operating room, Fiske spiked a fever of 101. He’d been zealous about wearing personal protection equipment, and was shedding his scrubs in the garage and showering in the basement for weeks, but he knew the risks. Because he was a doctor, he was able to get tested for the virus at the hospital where he worked, Overlook Medical Center in Summit.
He felt OK at first, and stayed in his basement. He advised patients and talked to his wife and high-school age sons by FaceTime. His friend and colleague, an infectious disease specialist named Meher Sultana, prescribed him the antibiotic Zithromax and the anti-malaria drug hydroxychloroquine, an unproven drug combination that has been used to help fight the virus.
But despite regular Tylenol, Fiske’s fever persisted, and Sultana and his dad, Steven, a gastroenterologist, didn’t like how he looked. On March 23, he went to the hospital.
His oxygen level was 91 percent, extraordinarily low for someone who was in such good shape. And although his lungs didn’t hurt, an X-ray revealed the double pneumonia. He went quickly to an isolated room with a sliver of a window from which a nurse, Kasey Welch, could monitor him from so she wouldn’t have to change her PPE every time she left his room. They, too, began to FaceTime.
Sultana prescribed intravenous fluids, Tylenol, and vitamin C, which did not help. He began to doubt he would survive, but his wife, Isabella, remained optimistic, summoning the memory of her Jewish grandmother, who’d survived the Holocaust in Poland by hiding in the woods with her sister and Isabella’s father. “Some people pray to God, I prayed to my grandmother,” she said.
Still, things were not looking good. It hurt to talk, and he labored even to shift positions in bed.
“He just wasn’t getting better, and he was starting to have a toxic look,” Sultana said. “I was getting very concerned about the possibility of permanent harm to his lungs.”
On March 25, she and Fiske’s father discussed the possibility of moving Josh to the intensive care unit and putting him on a ventilator, but that posed a separate array of dangers. The machines, while sometimes life-saving, can trigger a cascade of inflammation that leads to organ damage. Sultana found herself in the same position as doctors from China to Italy, from Spain to Argentina: fighting a virus that had been spreading in people for only for several months, and about which hardly anything was known. There was scant scientific literature to consult, and no playbook to follow.
Some doctors were discussing the possibility that many otherwise robust patients were experiencing cytokine storms. One key sign of that was the body’s levels of ferritin, a protein in the body that binds to iron.
Between admission on March 23 and the following day, Fiske’s ferritin skyrocketed from 1,712 to 4,316 micrograms per liter, more than 10 times the normal amount. His level of C-reactive protein, another indicator of inflammation and potential cytokine storm, was 15 times the normal reading.
Sultana was running out of options, and she had to act quickly. She researched the anecdotal reports on treatments with potential against the coronavirus. One was a powerful anti-inflammatory drug often used to treat rheumatoid arthritis, an autoimmune disease in which the immune system also goes into overdrive, attacking the body. She reasoned that Fiske might respond to this drug, called Actemra, which inhibits a particular cytokine called IL-6. Following promising results in China when the drug was used off-label in Covid-19 patients, the FDA had approved its use in U.S. clinical trials in March. (Reports from Italy using a similar drug, Kezvara, showed similar outcomes; it is now in global clinical trials.)
None of this is how medicine is supposed to be practiced in the data-centric 21st century, but Sultana and her colleagues across the world have found themselves flinging any plausible weapon at the virus.
“I couldn’t even lie to him and say, ‘You’re going to be OK,'” Sultana said.
Fiske’s father, 72, relied on more cinematic language to describe how he felt about the possibility he might lose his son. “I don’t panic easily,” Steven Fiske said. “But I was sad and scared for the first time in my medical career. I had to face the fact that medicine might not save my own son, who was another doctor.”
“This virus,” Steven Fiske said, “is a combination of ‘Alien,’ ‘The Day the Earth Stood Still,’ ‘The Andromeda Strain,’ and ‘Apocalypse Now.'”
On the morning of March 26, with Fiske’s fever still near 104, Welch gave him the infusion of Actemra. Within two hours, his fever dropped to 99 degrees and his oxygen levels returned to near normal.
It appeared the drug had worked. “You’re going to be fine,” Sultana reassured him by FaceTime.
Fiske stayed in isolation for four more days, improving daily and taking his own vitals so the nurses wouldn’t need to use more PPE. On March 30, Welch wheeled Fiske out of his room and into the lobby, where Isabella was waiting. For the first time, she allowed herself to cry.
He spent the next week in his basement, video-consulting with patients. On April 6, after 20 days without touching another person, he climbed the stairs and rejoined his wife and sons, ages 17 and 15.
Fiske has slowly resumed exercising, completing three 10-minute miles and a few sessions on his exercise bicycle. And last week, he returned to the office for the first time in a month. He is happy to be seeing patients in person again.
Soon, he is scheduled to return, as a surgeon, to the hospital where he was so recently treated. His experiences have shifted his perspective.
“I’ve never been nervous walking into a hospital before,” Fiske said. “I fought a war, and I’m going back to the same battlefield.”