As sweeping efforts to contain the COVID-19 pandemic go into effect around the globe, researchers are starting to get hints of just when patients are most contagious.
People infected with the SARS-CoV-2 virus, which causes the disease, may test positive for the virus both before and after they have symptoms. But a new study of nine people who contracted the virus in Germany suggests that people are mainly contagious before they have symptoms and in the first week of the disease.
Infectious viruses were isolated from about 17 percent of nose and throat swabs and more than 83 percent of phlegm samples during that first week, researchers report March 8 in a study posted at medRxiv.org.
Patients produced thousands to millions of viruses in their noses and throats, about 1,000 times as much virus as produced in SARS patients, Clemens Wendtner, director of infectious disease and tropical medicine at Munich Clinic Schwabing, a teaching hospital, and his colleagues found. That heavy load of viruses may help explain why the new coronavirus is so infectious.
Scientists identified these nine people some time after they had been exposed to the coronavirus, so researchers don’t know for sure when exactly people begin giving off the virus.
After the eighth day of symptoms, the researchers could still detect the virus’s genetic material, RNA, in patients’ swabs or samples, but could no longer find infectious viruses. That’s an indication that antibodies that the body’s immune system makes against SARS-CoV-2 are killing viruses that get out of cells, Wendtner says.
The study brings an important point to light; finding RNA or pieces of a virus in a swab or sample is no guarantee that the virus is “live,” or infectious, says Ali Khan, dean of the College of Public Health at the University of Nebraska Medical Center in Omaha. “Some of it is discouraging news because when you are mildly [ill] or just [getting] sick, you’re putting out a whole lot of virus, which explains why we’re seeing so much transmission within our communities,” says Khan, was not involved in the study.
But there’s encouraging news, too. Plummeting numbers of infectious virus after antibody production turns on “means that after about 10 days or so, you’re not likely to be infecting other people,” Khan says. Other studies also suggest that people with very mild or asymptomatic infections don’t shed as much virus and aren’t as likely to infect other people as people with more severe cases, he says.
Wendtner and colleagues put the nine patients through tests every morning during their hospital stay, collecting blood, urine, stool, nasal and throat swabs and asking the people to cough up sputum, or phlegm. “We were learning with the patients because we did not know when would be the best and safest time to discharge them,” Wendtner says.
The high levels of virus shedding from the nose and throat happened very early in infection — by the time of testing, most patients’ upper airway virus production had already peaked. As the infection progresses, the virus moves deeper into the lungs, the findings suggest.
The team never found evidence of the virus in blood or urine and has stopped collecting those samples from a “second wave” of 23 COVID-19 patients now being treated at the hospital. Researchers did detect viral RNA in feces, but no infectious virus there. That suggests that the virus isn’t spread through stool, an unknown until now.
All nine patients are employees of Webasto, an auto supplier in Stockdorf. They caught the virus from a male coworker, who became known as Patient 1. He originally got the virus from a business colleague from Shanghai who came to Germany in January for a series of meetings (SN: 1/31/20). Both Patient 1 and his Shanghai colleague transmitted the virus before developing symptoms, the first documented cases of asymptomatic spread.
As health officials tested other employees of the company, they found the study participants and placed them in isolation at the Munich clinic. In one case, Patient 1 sneezed during a meeting with one person, Wendtner says. “That was enough for infection.” In other cases, “they had simple business meetings, sitting together for 60 minutes, 90 minutes [at a table or] in front of a computer, with no physical contact — just one handshake, that’s all,” Wendtner says. “The infectivity is quite high.”
Most had coughs, but only two developed a fever, the most common symptom reported in other studies. Most symptoms were mild and one person never developed any at all. One patient developed severe pneumonia.
Two of the nine had runny noses, previously reported as a rare symptom of COVID-19. Another four had stuffy noses and reported that they couldn’t smell or taste anything. “In all of our patients, it cleared up, but it was a little bit annoying for two weeks or so,” Wendtner says. “They could order anything they wanted [to eat], but [if] you can’t taste it, it doesn’t matter.”
A temporary lack of smell or taste also affected some SARS patients in 2003, he says. That symptom may indicate that in addition to causing swelling in the nose, the virus may infect nerve cells responsible for identifying odors, he says.
Patients in the study started making antibodies against the virus about six to 12 days after symptoms started. Once antibody production kicked in, researchers still found high levels of viral RNA in phlegm and in nose and throat swabs, but patients were no longer giving off infectious virus.
The early and extreme contagiousness of the virus “tell us that gatherings of people should be avoided,” Wendtner says. But the results also may suggest that isolation periods could be shorter for people who have RNA but no virus. Researchers thought that because tests could still detect RNA for up to weeks after symptoms had cleared (SN: 2/28/20), patients were infectious for that long. Most patients are not released from the hospital until two separate tests within 24 hours come back negative, Wendtner says.
But Wendtner isn’t suggesting letting people out of quarantine before their two weeks are up. “Fourteen days is safe, and you have to keep it simple,” Wendtner says. “Maybe it’s safe 10 days after symptoms start, but you have to prove they have those neutralizing antibodies.” Tests for the antibodies, however, are not widely available.