We Still Don't Fully Understand The Label 'Asymptomatic'

Even if someone is infected by the novel coronavirus and remains asymptomatic — free of coughing, fever, fatigue and other common signs of infection, that doesn't mean the coronavirus isn't taking a toll. The virus can still be causing mild — although likely reversible — harm to their lungs.

A new paper in Nature Medicine, published June 18, documents the clinical patterns of asymptomatic infections. It finds that many of the people studied developed signs of minor lung inflammation — akin to walking pneumonia — while exhibiting no other symptoms of the coronavirus.

The study shows that being asymptomatic doesn't always mean that no damage has occurred in someone's body; follow-up studies will help researchers assess for potential long-term impacts. It also demonstrates that the intense scrutiny applied to novel coronavirus infections could shed light on how other respiratory diseases operate: Asymptomatic carriers of flu or common cold viruses are not studied much, so it's unclear whether the documented inflammation is a typical immune response or specific to the novel coronavirus.

The percentage of people with asymptomatic infections is unclear. "Estimates suggest that anywhere between 6% and 41% of the population may be infected but not have symptoms," Maria Van Kerkhove, a top World Health Organization official, said June 9.

Asymptomatic coronavirus carriers are hard to find and study — because people usually get tested for the coronavirus only if they think they may have it. And some people who appear asymptomatic at first do later develop classic symptoms such as high temperatures, fatigue and difficulty breathing.

The Nature Medicine paper analyzes 37 asymptomatic cases, found through the contact tracing and testing efforts of the Wanzhou District Centers for Disease Control and Prevention in central China, which screened 2,088 close contacts of coronavirus patients from February through early April.

The asymptomatic patients were hospitalized for observation. Fifty-seven percent showed lung abnormalities on a CT scan, a sensitive imaging technique that produces a three-dimensional picture of the lungs. Some showed "striped shadows," while others presented with "ground-glass opacities" — clear signs of inflammation in the lungs.

"To find so many asymptomatic patients with such significant changes on CTs is quite surprising," says Dr. Alvin Ing, a professor of respiratory medicine at Macquarie University who was not involved with the study. It shows that even people with no outward signs of infection can be experiencing some temporary damage to their lungs. It feeds into a pattern he's seen in treating COVID-19 patients: "The symptoms underestimate the severity of the disease." In other words, the coronavirus is often taxing a person's body more severely than their symptoms — or lack thereof — suggest.

The findings are consistent with several studies following asymptomatic patients in China, which have found that many can develop lesions in the lungs despite having no outward symptoms, says Dr. Jennifer Taylor-Cousar, a pulmonologist at National Jewish Health in Denver not involved with the paper. "It probably is, at least in this disease, pretty common," she says.

Doctors in New York have seen similar patterns. Dr. Jorge Mercado, a pulmonologist and critical care doctor at NYU Langone Hospital-Brooklyn who is not affiliated with the study, says he's seen many instances where a patient has come to the hospital for an issue not related to COVID-19 and tested positive for the coronavirus. "Those patients evolved into what this paper illustrates, which is [their coronavirus infections] causing pneumonia, causing inflammatory changes," he says.

Still, Taylor-Cousar cautions that researchers are studying the new coronavirus more intensively than they've studied other respiratory ailments. "Usually if someone is asymptomatic [with a common cold or flu virus], we would never even see them at all," she says, "and we would never think to get a CT scan on them." So there's no comparable data to say whether the lung abnormalities are specific to asymptomatic coronavirus carriers, or common among respiratory viruses.

The patterns of lung disease seen on the CT scan can be caused by several factors. "It can be a little bit of fluid in the lungs, sometimes a little blood in a lung or sometimes just a small area of inflammation in the lung," says Dr. Neil Schluger, chief of pulmonary, allergy and critical care medicine at the Columbia University Medical Center. "When I look at these images, I see what to me looks like small areas of inflammation that we see with many kinds of lung infections."

For asymptomatic cases with mild lung inflammation and no other signs of illness, pulmonologists say they're likely to kick the infection quickly and see no lasting lung damage.

"I suspect that, if you followed up with these asymptomatic people in several months, most of their CT scans would be completely normal unless they were known to later develop symptoms," Taylor-Cousar says.

In the midst of an infection, however, doctors can't predict how an individual's case will progress. "There's no way to know who is going to stop with an asymptomatic infection and likely recover completely and who is likely to go on to more severe infection," Schluger says.

The Nature Medicine study also found pieces of the coronavirus in swab samples from asymptomatic patients for an average of 19 days — five days longer than a control group of mildly symptomatic patients. While it doesn't necessarily mean asymptomatic people are infectious the whole time, it does suggest they're capable of spreading the virus to others at some point in their infections, Schluger says. "As we reopen society, that's why it's so important for people who are going out to wear a mask," he says.

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