These patients don’t struggle to breathe—but COVID-19 is still starving them of oxygen

One alarming symptom robs many patients of blood oxygen well before they notice. Doctors are racing to understand it.

Tuesday, May 19, 2020,
By Maya Wei-Haas
Photograph by George Washington Hospital and Surgical Theater

Standing in her patient’s living room, Mari Seim was perplexed. The man, in his 60s, had fallen ill with flu-like symptoms more than a week before. His breathing rate had climbed, so his daughter called the Taarnaasen Medical Centre, the clinic where Seim works as a general practitioner, just outside Oslo, Norway. With COVID-19 at the forefront of her mind, Seim set out to check on the man, and she wasn’t prepared for what she found.

“He was sitting in a chair, and he was smiling,” she says. “He didn’t seem bothered in any way.”

Yet his breaths came in rapid succession, nearly triple the normal rate. A faint blue tinted his lips and fingers. She truly didn’t grasp how sick he was until she measured the oxygen levels in his blood. A normal percentage would sit well above 90. The number Seim saw was 66. For a split second, Seim thought she had the device turned upside down. She checked again. The reading was the same, and she immediately called an ambulance.

The patient had what seems to be a pervasive but initially overlooked feature of COVID-19: silent hypoxia. Unlike many other respiratory diseases, COVID-19 can slowly starve the body of oxygen without initially causing much shortness of breath. By the time some patients have trouble breathing or feel pressure in the chest—among the symptoms the U.S. Centres for Disease Control and Prevention lists as emergency warning signs—they are already in dire straits.

Silent hypoxia has surprised many doctors. Some patients are running so low on oxygen, health-care workers would normally expect them to be incoherent or in shock. Instead, they’re awake, calm, and responsive. They chat with the physicians. They use their mobile phones. While the basic physiology behind why these patients don’t immediately feel short of breath is well understood, scientists are still trying to come to grips with exactly how COVID-19 ravages the body, and why this disease, in particular, can quietly take your breath away.

The roots of breathlessness

Frequently, breathlessness parallels the loss of elasticity in the lung tissue. Many respiratory diseases can stiffen the lungs, due to inflammation, scarring, or the buildup of fluid and pus. That stiffening can hinder the movement of the bellows in our chest, creating a sensation of air being squeezed from the body.

Lung stiffness also impacts a patient’s ability to expel carbon dioxide, and the buildup of this gas is a potent trigger for our urge to inhale. The body’s levels of carbon dioxide usually sit in a narrow range. If CO2 increases, your brain gets an emergency alert—that’s the feeling of breathlessness.

For many COVID-19 patients, it seems neither of these triggers are pulled at the disease’s onset, says Cameron Baston, a pulmonary and critical care physician at Penn Medicine. Early in the course of the disease, many patients’ lungs remain stretchy, like a balloon, so they can breathe freely in and out. As their oxygen levels slowly decline, their breathing rate gradually increases to compensate, which blows out loads of the body’s carbon dioxide. The result is a sneaky onset of hypoxia, with some patients developing dangerously low levels of oxygen without the increases in carbon dioxide that would commonly alert the body to the problem.

“In almost all clinical experience that physicians have, problems with the lung involve both problems with oxygen absorption and carbon dioxide elimination,” says Richard Levitan, an emergency physician who volunteered to spend 10 days treating COVID-19 pneumonia at New York’s Bellevue Hospital. “This disease is different.”

“The cause, and therefore the treatments, behind high-altitude diseases and COVID-19 are vastly different – contrary to some claims circulating online.”

Doctors have previously observed silent hypoxia among high-altitude climbers and pilots, Levitan notes. As you ascend into the skies, the atmospheric pressure drops, which means fewer oxygen molecules are available for any given breath, yet rapid breathing still expels carbon dioxide. He stresses that the cause, and therefore the treatments, behind high-altitude diseases and COVID-19 are vastly different, contrary to some claims circulating online. But one of the body’s reactions to this reduced oxygen—breathing faster—is similar.

This process has also been studied in pilots, who train in low-oxygen (hypobaric) chambers to recognise the subtle symptoms of silent hypoxia, in case the cabin depressurises while flying, says William Ottestad, who specialises in hypobaric medicine as a doctor for the Norwegian Special Operations Command. “It’s also been coined the silent killer because of its insidious character,” he adds. That’s because a sudden drop in cabin pressure can cause pilots to fall unconscious and crash.

In these cases, the low carbon dioxide levels that result from rapid breathing cause oxygen to bind more strongly to hemoglobin, the protein that carries oxygen within red blood cells. This means more oxygen can be delivered to tissues in need, as long as the heart continues to pump strongly, explains Ottestad, who is also an anaesthesiologist with Oslo University Hospital’s air ambulance department.

The COVID-19 experience may parallel what happens in pilots. The rapidly breathing patients frequently retain decent heart function early in the disease, and thus still have the ability to pump blood to their extremities. Ottestad speculates that without their low carbon dioxide levels, COVID-19 patients would perhaps suffer from even lower oxygen levels than measured, which could make a severe case of the virus even worse.

There have not yet been thorough studies of whether early detection of silent hypoxia can improve COVID-19 outcomes. But prolonged hypoxia may strain the heart and perhaps other bodily systems, and Baston points to the improved life expectancies for patients with chronic obstructive pulmonary disease (COPD) who are given supplemental oxygen.

Breathing under the microscope

For now, much remains unknown about how the coronavirus causes silent hypoxia, Ottestad says. “We are all kind of baffled by this.” But hypotheses exist.

One hinges on the fact that oxygen moves from the lungs to the blood by transiting from tiny air sacs known as alveoli to the blood vessels. SARS-CoV-2, the virus behind the pandemic, invades by attaching spikes on its viral surface to protein receptors scattered on top of cells called ACE2, which are abundant throughout the lungs and their many air sacs. Once the germ establishes itself in enough cells, the ensuing battle between the body’s immune response and the virus sparks a torrent of damage.

Such an effect could hinder the passage of oxygen from alveoli to the blood, while carbon dioxide—which passes much more readily from the blood out through the lungs—is less impacted, Ottestad says. He points to two small autopsy studies that suggest COVID-19 causes early-onset inflammation of the tissues around the alveoli.

Another possibility may be that the disease creates a mismatch between oxygen’s movement in the lungs and the flow of blood, says pulmonologist William Janssen, the head of critical care medicine at National Jewish Health. Usually, blood vessels constrict so that the flow is greatest to highly aerated regions of the lung, where oxygen is picked up, and lowest to areas lacking airflow. But this safeguard could be abnormal in COVID-19 patients, meaning more blood is flowing to damaged lung areas, while less is passing through healthy parts.

Blood flow to oxygen-rich zones of the lung might alternatively be hindered by tiny clots in the blood vessels, notes Enid Neptune, a pulmonary and critical care specialist at Johns Hopkins Medicine. Many have pointed to elevated blood clotting as a possible deadly facet of COVID-19. Some doctors are debating the use of blood thinners in COVID-19 patients to prevent clotting, but Janssen cautions that larger trials should be conducted before this practice becomes the norm.

What’s more, the mechanism behind silent hypoxia as seen with COVID-19 may not be unique to the disease, says Penn Medicine’s Baston, who works with patients suffering from particularly severe and rare lung diseases. While uncommon, some of his past patients have become silently hypoxic from other illnesses, such as bacterial pneumonia.

“What COVID-19 has done is taken things that we see and pushed it into every community hospital across the country,” Baston says.

Worried about silent hypoxia?

The curious presentation of COVID-19 has led many health-care professionals to search for more effective routes for treatment. Many now suggest holding off on using mechanical ventilation for patients unless their condition is advanced. Instead, they are trying less invasive supportive care early on, such as supplemental oxygen and placing patients in a prone position on their bellies to allow for better oxygen flow.

Levitan says that raising awareness of this silent symptom of COVID-19 could help by getting people to head to a hospital earlier in the course of disease, before they decline severely and require mechanical ventilation. A simple, at-home gadget known as a pulse oximeter could help people who develop other symptoms to also monitor for silent hypoxia, Levitan says.

“This is not a panacea. It’s not going to prevent all death,” he says. But “we need to give people a sense of hope and more information, so they can wrap their head around what’s happening.”

A collaboration among multiple Norwegian health-care centres and a Spanish university is recruiting COVID-19 patients for a study using an array of biosensors, including pulse oximetry, for remotely tracking patients’ conditions. The hope is to potentially catch patients early in the disease’s progression, as well as reduce the need for patients with mild cases to remain in medical centers for extended periods.

Other doctors generally agree that use of a home pulse oximeter is useful for monitoring disease progression. But Janssen stresses that this should be done in consultation with a medical professional. As fear of COVID-19 spread, he worries that patients have been afraid to enter medical care centres and possibly risk catching the disease, curbing lines of communication to doctors and encouraging self-diagnosis.

He gives one simple piece of advice: “If you're sick, call your doctor.”

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