RECOVERED FROM COVID-19 BUT WITH AN UNCERTAIN FUTURE

By broadcasting his journey on social media, Chow had hoped to make the best of a bad situation. But it didn’t take long before his tweets became shorter and the time between them longer. His fight against the illness had become more grueling than he ever anticipated.

Twenty-four hours earlier, the idea that he could have COVID-19 hadn’t crossed his mind. He had a terrible cough but figured he was sick with a run-of-the-mill illness his kids had brought home from school. A physician friend he had been in touch with, however, grew concerned. At his urging, Chow took stock of the situation with a pulse oximeter, a small, inexpensive medical device he happened to have at home. After attaching it to his finger to measure his blood oxygen, the screen blinked “70%”—dangerously lower than the 85% reading that warrants a trip to the hospital.

His wife rushed him to the emergency department (ED) but despite receiving supplemental oxygen, he was still gasping for air. Within hours, doctors transferred him to the medical intensive care unit (MICU) where they could monitor him more closely. There, a high-flow machine pushed oxygen into his body at up to 12 times the rate he was given in the ED. Only then did he feel relief.

“I could literally feel the oxygen flowing through to my extremities,” Chow says. “I thought, ‘This is what breathing feels like.’”

With symptoms ranging from nonexistent (asymptomatic) to deadly, perhaps one of the most puzzling aspects of COVID-19 is the unpredictability of how the disease unfolds for each person. As a father with two young children, Chow doesn’t fit the stereotype of the nearly 10% of infected people who need hospitalization. He is at least 27 years younger than the age group at highest risk and doesn’t have any of the long list of medical conditions that could shift a lower-risk person into a more vulnerable category.

Researchers at U of U Health are investigating whether genetics or drug interactions could play a role, or if they can uncover unique susceptibilities. In time, such information could more precisely pinpoint who is prone to complications.

As a hospitalist at U of U Health, Natalie Como, MD, has encountered a lot of viral infections. But she says COVID-19 is “like nothing I’ve ever seen.” What’s particularly striking to her is how ill COVID-19 can make otherwise healthy, active people. And once it grabs hold, it doesn’t let go.

Typically, ICU patients remain in that wing of the hospital for three days on average. In contrast, the average ICU stay for COVID-19 patients at U of U Health is 10 days; a rare few have needed intensive care for months.

Besides providing oxygen, either through a high-flow device like Chow had or through a more invasive breathing machine—the ventilator—there is not much that health care providers can do to speed recovery.

Chow remained “stuck” on a dangerous plateau, relying on high-flow oxygen for days. But for him—and for the sickest patients who remain on a ventilator for days or weeks—that seemingly stagnant phase masks a dynamic battle happening inside.

A desire to improve the prospects of her patients drives critical care physician Elizabeth Middleton, MD, to carry out research that sees the unseen. “Caring for these patients opens up all kinds of questions about what is going on mechanistically and how we can improve outcomes with targeted therapies,” she says.

Together with U of U Health physician-scientists Christian Con Yost, MD, and Joshua Schiffman, MD, their team discovered that an out-of-control immune response could be causing complications. Ordinarily web-like NETs (Neutrophil Extracellular Traps) are beneficial, capturing and killing invading pathogens like viruses. But in COVID-19, the mechanism becomes hyperactive and may trigger abnormal blood clotting, potentially leading to organ failure in the worst cases.

“This could be a brand-new area of pathobiology that could shed a light on COVID-19 morbidity and mortality,” Schiffman says. Experiments in the lab show that a peptide from umbilical cord blood quiets the highly active immune response. In his role as CEO of PEEL Therapeutics, Schiffman is now evaluating whether the natural chemical can one day be used as a therapy for patients.

Their colleagues in internal medicine led by Robert Campbell, PhD, also called upon Middleton. That collaboration led to the discovery that multiple genetic changes in circulating cells, called platelets, may also contribute to an abnormal inflammatory response and worsening COVID-19.

These findings are the tip of the iceberg. Some patients also sustain damage to the heart, gastrointestinal system, kidneys, and liver; there are reports of stroke and seizures. At this point it is hard to parse whether these impacts come from uncontrolled inflammation or are a direct effect of the virus.

Even treatment itself has downsides. While the ventilator undoubtedly saves the lives of people who are severely ill with COVID-19, extended use of sedatives that allow patients to tolerate a tube lodged in their airway can cause delirium and memory loss that persist after recovery. Plus, the longer someone is immobilized, the more that muscles waste away, vessels clot and eventually organs malfunction. With COVID-19 patients lingering on ventilators, lasting side effects are a concern.

“The physical and mental toll is not small,” says pulmonologist Scott Aberegg, MD, who has treated patients with the disease in Utah and during the surge in New York City in April. There, he saw patients emerging from the ICU barely able to string a sentence together. “Only time will tell what the long-term effects will be.”