COVID-19 can be spread before it causes symptoms, when it produces symptoms like those of the common cold, and as many as 12 days after recovery, according to a virologic analysis of nine infected patients published today on the preprint server medRxiv.

Also, in a study published in today's Annals of Internal Medicine, researchers at Johns Hopkins found a median incubation period for COVID-19 of 5.1 days—similar to that of severe acute respiratory syndrome (SARS).

Virus concentrates quickly, sheds efficiently

Led by researchers in Germany, the virologic study, which has not yet been peer-reviewed, found that the novel coronavirus quickly begins producing high viral loads, sheds efficiently, and grows well in the upper respiratory tract (nose, mouth, nasal cavity, and throat).

"Shedding of viral RNA from sputum outlasted the end of symptoms," the authors wrote. "These findings suggest adjustments of current case definitions and re-evaluation of the prospects of outbreak containment."

The nine patients, who were admitted to the same Munich hospital, were studied because they had had close contact with an index case. Cell cultures and real-time polymerase chain reaction (RT-PCR) were done on throat swabs and samples of sputum, stool, blood, and urine. Throat swabs showed very high viral shedding during the first week of symptoms.

The findings contrasted starkly with those from the 2003 outbreak of SARS in terms of viral load. "In SARS, it took 7 to 10 days after onset until peak RNA concentrations (of up to 5x105 copies per swab) were reached," the researchers wrote. "In the present study, peak concentrations were reached before day 5, and were more than 1,000 times higher."

Throat swabs were much more sensitive with COVID-19 than with the SARS virus, and the virus was easier to isolate. Seven of the nine patients had upper respiratory infection.

Social distancing to prevent infection

Michael Osterholm, PhD, MPH, director of the Center for Infectious Disease Research and Policy at the University of Minnesota, which publishes CIDRAP News, said that the results challenge the World Health Organization's assertion that COVID-19 can be contained.

The findings confirm that COVID-19 is spread simply through breathing, even without coughing, he said. They also challenge the idea that contact with contaminated surfaces is a primary means of spread, Osterholm said.

"Don't forget about hand washing, but at the same time we've got to get people to understand that if you don't want to get infected, you can't be in crowds," he said. "Social distancing is the most effective tool we have right now."

Data generally back 2-week quarantine

The Johns Hopkins study used news reports and press releases to analyze the demographics and dates and times of possible exposure, emergence of symptoms, fever onset, and hospitalization of 181 patients with confirmed COVID-19 infection outside Hubei province, China, from Jan 4 to Feb 24.

The researchers estimated the median incubation period at 5.1 days (95% confidence interval [CI], 4.5 to 5.8 days). They found that 97.5% of patients who have symptoms do so within 11.5 days of infection (CI, 8.2 to 15.6 days).

After the recommended 14-day quarantine or active monitoring period, "it is highly unlikely that further symptomatic infections would be undetected among high-risk persons," the authors wrote. "However, substantial uncertainty remains in the classification of persons as being at 'high,' 'medium,' or 'low' risk for being symptomatic, and this method does not consider the role of asymptomatic infection."

Understanding how long active monitoring is needed to limit the risk of missing COVID-19 infections is important for health departments faced with limited resources. The results support current proposals for length of quarantine or active monitoring of people who may have been exposed to [COVID-19], "although longer monitoring periods might be justified in extreme cases," they wrote.

In a Johns Hopkins news release today, senior author Justin Lessler, PhD, an associate professor in the Bloomberg School's Department of Epidemiology, said, "The current recommendation of 14 days for active monitoring or quarantine is reasonable, although with that period some cases would be missed over the long-term."

Of the 181 patients, 69 (38%) were female, 108 were male (60%), and 4 (2%) were of unknown sex. Median age was 44.5 years. Cases were collected from 24 countries and areas outside mainland China (108 cases) and 25 provinces in mainland China (73 cases).

The researchers noted that publicly reported cases may overrepresent severe cases, which may have a different incubation period than that of mild cases.