How Many Total Coronavirus Cases, Including Undiagnosed?

pread of the novel coronavirus SARS-CoV-2 from Hubei Province, China prior to travel restrictions imposed on January 23 likely seeded a million cases worldwide so far, many so mild that people might not have realized they were infected.

MARCH 22, 2020 -- Spread of the novel coronavirus SARS-CoV-2 from Hubei Province, China prior to travel restrictions imposed on January 23 likely seeded a million cases worldwide so far, many so mild that people might not have realized they were infected, according to findings published online today in the journal Science.

Researchers discussed the findings of the new study and a previously posted study on the effect of travel restrictions during a news conference today.

In the Science article, Ruiyun Li, PhD, from the MRC Centre for Global Infectious Disease Analysis, Imperial College London, UK, and colleagues used mathematical modeling that combined data on people's movements among 375 Chinese cities with reported infection data, using statistical inference techniques.

The analysis suggests that before travel restrictions were instituted in Wuhan, 86% of cases were undocumented. The model also estimates that these undetected cases were 55% as contagious as were documented infections.

"Six out of seven cases are undocumented. The majority of cases are mild, with few or no symptoms, so most people may think they have a cold or not recognize that they're ill. If globally 150,000 are confirmed, then it's not unreasonable to project that we're approaching close to a million infections globally," said senior author Jeffrey Shaman, PhD, from the Mailman School of Public Health at Columbia University, New York City.

That also means that the 3500 or so documented cases in the United States are likely the tip of an iceberg.

The travel restrictions imposed in late January might have had only a limited effect, said Elizabeth Halloran, MD, DSc, director of the Center for Inference and Dynamics of Infectious Diseases at the Fred Hutchinson Cancer Research Center in Seattle, Washington and a coauthor of the earlier study, posted on medRxiv preprint server. (Articles posted on the medRxiv server, including the one on travel restrictions, have not been peer-reviewed.)

"Travel restrictions alone do not do much to delay the spread of the disease. Reducing transmissibility is really the key," she said.

Other speakers concurred.

"Travel restrictions are useful to delay the spread of the disease, but the epidemic is already seeded in the US and we're seeing ongoing local transmission in many states, and will see more with more testing," said Alessandro Vespignani, PhD, a professor and computer scientist at Northeastern University in Boston, Massachusetts, and a coauthor of the travel restrictions paper. But travel restrictions might delay progression in some places and provide time for preparing.

"We need to have strong transmission reduction in local places, in the communities where it is already seeded," he added.

One of many unknowns is seasonality of coronavirus infections. The speakers agreed that even if heat and humidity dampen down the disease come summer, the effect could be minimal, given the huge numbers of infected people. For influenza, for example, "Numbers may go down but not go away in the summer months," Shaman said. A confounding factor in analyzing summertime reprieves from infectious diseases is school vacation, which could reduce transmission, several speakers mentioned.

"We're looking at a very infectious disease, even if seasonality does bring it down," Halloran said. She added that perhaps summer may decrease the average number of people to whom an infected person spreads the disease, dropping it from the present 2.5 toward 1.

The speakers also discussed treatments on the horizon. "A number of antivirals and monoclonal antibody-based drugs are in clinical trials, so we [may have] effective therapeutics to treat the severe cases," said Ira M. Longini Jr, PhD, from the department of biostatistics at the University of Florida, Gainesville, and a coauthor of the travel restrictions paper.

ClinicalTrials.gov currently lists 96 entries for COVID-19 treatments. The list of agents being tested includes potentially repurposed antivirals and monoclonals, as well as mesenchymal stem cells, vitamin C, nitric oxide, corticosteroids, thalidomide, sildenafil, and chloroquine.

Vaccine development is underway too. "Only a vaccine can really control the epidemic to a large extent by reducing the susceptibility of vaccinated people and reducing transmissibility to others," said Longini. And a vaccine may be especially critical because there is evidence from other coronaviruses that immunity may not be durable, he added, with the caveat that he's only heard anecdotal evidence for this new virus.

Serological testing will also be needed to identify people who have developed immunity, several speakers mentioned.

As the weeks turn into months for the pandemic, the role of testing will evolve, Shaman explained. "Early on, as an outbreak appears in a local community, proactive testing may be beneficial and quickly identify the scale, and the need to implement social distancing, isolation, and quarantine to reduce person-to-person transmission. But once we are past the point at which hospitals become inundated, like in Italy, testing may be beside the point. We'd still have to implement social distancing, isolation, and quarantine to bring the situation under control, as they have in China."

"Our findings underscore the seriousness and pandemic potential of SARS-CoV-2. If the novel coronavirus follows the pattern of 2009 H1N1 pandemic influenza, it will also spread globally and become a fifth endemic coronavirus within the human population," the researchers conclude.

A limitation of the study reported is extension to other countries, which likely have different control, surveillance, and reporting practices.

Science. Published online March 16, 2020.

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