“That day, I suddenly couldn’t breathe,” said the 26-year-old customer service representative from Flint, Mich. An ambulance took her to the hospital, where she spent eight days, four of them in intensive care, before she recovered and was able to go home.
For people who suffer the most severe reactions to the novel coronavirus — and their caregivers — the second week of the disease can become a time of sudden peril and heightened concern, when some of those who seem stable or mending can suddenly become critically ill.
There is little consensus among doctors and experts about why days five through 10, or thereabouts, seem to be so dangerous for some people with covid-19, the disease caused by the virus. But everyone from critical care specialists to EMTs is aware of this frightening aspect of the disease.
“This second-week crash has certainly been well described, but two-and-a-half months in, why it happens we’re still not entirely sure,” said Ebbing Lautenbach, chief of the division of infectious diseases at the University of Pennsylvania’s Perelman School of Medicine.
There is little, if any, current research to guide them.
“I’ve been thinking about this a lot,” said Naftali Kaminski, chief of pulmonary critical care and sleep medicine at the Yale School of Medicine, who studies the genomics of lung disease. “There’s an early stage of infection and the virus sits somewhere. You can almost look at the virus as a fifth column coming in, securing its stronghold and then slowly inducing more cells to let it in.
“Because of this lurking nature, your genetic makeup and preexisting conditions will affect presentation of the disease,” he said.
Doctors say the overwhelming majority of covid-19 cases do not require hospitalization. According to the Centers for Disease Control and Prevention, U.S. covid-19 patients are currently hospitalized at a rate of 29.2 per 100,000 people, or just under 10 percent of the 1 million known cases so far. Of those, only a small percentage require intensive care or ventilators, and only some will experience a rapid downturn in their health.
But people with the coronavirus can crash before or after they are hospitalized. Doctors report seeing patients who wait too long to seek care, including those who do not feel the symptoms of plummeting oxygen levels, such as shortness of breath, until they are in crisis. No one is sure why. Many people’s lungs remain flexible for a while, allowing carbon dioxide out and forestalling the sensation they aren’t getting enough oxygen.
“The people who actually crash, they’ve actually been sick a while,” said Merceditas Villanueva, an associate professor of medicine at the Yale School of Medicine. “They’ve underestimated how sick they are, or they’ve just waited.”
The virus may be killing the cells that line the air sacs of the lungs, which keep them open and allow for the exchange of oxygen and carbon dioxide, said Russell G. Buhr, a pulmonary and critical care physician at Ronald Reagan UCLA Medical Center in Santa Monica, Calif.
At some point, the body simply can’t regenerate those cells as quickly as they die, he said, and a stable situation turns life-threatening. That may also help explain why covid-19 patients can linger on ventilators for up to four weeks, much longer than in other respiratory diseases, he said.
“Some of that may be direct lung toxicity effect,” Buhr said. “You need more time to regenerate those cells.”
Another line of thought focuses on the virus’s possible effect on the cardiovascular system. Researchers have suggested that some crashes are caused by events such as heart attacks, strokes and clots related to blood complications.
Eytan Raz, a neurointerventional radiologist at NYU Langone Health, said one theory is that some of the blood clotting complications may be due to an over-reactive immune response that comes after the virus has settled in, multiplied and triggered a defensive army of antibodies to fight back.
An April 17 paper in the medical journal, The Lancet, said that covid-19 appears to have the ability to attack the lining of blood vessels anywhere in the body. Frank Ruschitzka, a researcher from University Hospital Zurich, and his co-authors wrote that this may be why so many organs, including the lungs, kidneys and intestines, are affected in patients with severe illness.
It also could explain why people with cardiovascular disease, diabetes and obesity, as well as smokers, are more likely to have severe illness.
Michael Bell, chief of critical care at Children’s National Hospital, speculated that this is why the second week crash and covid-19 itself, are rarely seen in children.
“We’ve had several dozen kids on our medical floor and have been on pins and needles that they were going to have a big collapse after week one. We haven’t seen any of that,” he said. “My best explanation is children in general have pretty healthy blood vessels.”
Ventilators themselves also may contribute to the crash, Buhr said, especially in overwhelmed hospitals where doctors cannot spend enough time fine-tuning the devices that force oxygen into the lungs. Too much pressure on inflamed lungs can produce more of the inflammatory response to the coronavirus, worsening the clogging of air sacs called alveoli.
“We don’t like to talk about that one as much, but treatment of critically ill people is very complicated,” Buhr said. “Ventilators don’t work like meds. Adjusting the ventilator requires a lot of hands-on effort. And, in particular when hospitals are under stress, it’s much more difficult to provide that level of care.”
Within the field, a debate has broken out about whether physicians are turning to ventilators too often and too early, driven by the traditional response to remarkably low blood oxygen levels in some patients who show none of the symptoms of oxygen deprivation. Some doctors have advocated a more conservative initial response that would spare more patients the sedation, intubation and side effects of mechanical ventilation.
Aware of the hazards of the second week of the disease, hospitals have employed a number of tactics. Some are putting patients on oxygen earlier and using blood thinners prophylactically to prevent clots. At UCLA, caregivers more aggressively monitor ventilator pressure and use proning — placing patients on their stomachs — as much as 16 hours a day, Buhr said. The technique has been shown to increase the amount of oxygen getting into the lungs of patients with Acute Respiratory Distress Syndrome, a hallmark of severe covid-19.
Many of these specialists expect to continue adjusting their approach to the disease and to the unpredictability of its second week.
“There’s a lot that we don’t know,” Villanueva said.
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