Whole-town study reveals more than 40% of COVID-19 infections had no symptoms

A study of COVID-19 in the quarantined Italian town of Vò, where most of the population was tested, reveals the importance of asymptomatic cases.

The authors of the new research, from the University of Padova and at Imperial College London, published today in Nature, suggest asymptomatic or pre-symptomatic people are an important factor in the transmission of COVID-19. They also argue that widespread testing, isolating infected people, and a community lockdown effectively stopped the outbreak in its tracks.

The town of Vò, with a population of nearly 3,200 people, experienced Italy's first COVID-19 death on 21 February 2020. The town was put into immediate quarantine for 14 days. During this time, researchers tested most of the population for infection of SARS-CoV-2, the virus that causes COVID-19, both at the start of the lockdown (86 percent tested) and after two weeks (72 percent tested).

The testing revealed that at the start of the lockdown, 2.6 percent of the population (73 people) were positive for SARS-CoV-2, while after a couple of weeks only 1.2 percent (29 people) were positive. At both times, around 40 percent of the positive cases showed no symptoms (asymptomatic). The results also show it took on average 9.3 days (range of 8-14 days) for the virus to be cleared from someone's body.

None of the children under ten years old in the study tested positive for COVID-19, despite several living with infected family members. This is in contrast to adults living with infected people, who were very likely to test positive.

As a result of the mass testing any positive cases, symptomatic or not, were quarantined, slowing the spread of the disease and effectively suppressing it in only a few short weeks.

Co-lead researcher Professor Andrea Crisanti, from the Department of Molecular Medicine of the University of Padua and the Department of Life Sciences at Imperial, said: "Our research shows that testing of all citizens, whether or not they have symptoms, provides a way to manage the spread of disease and prevent outbreaks getting out of hand. Despite 'silent' and widespread transmission, the disease can be controlled."

The results of the mass testing programme in Vò informed policy in the wider Veneto Region, where all contacts of positive cases were offered testing. "This testing and tracing approach has had a tremendous impact on the course of the epidemic in Veneto compared to other Italian regions, and serves as a model for suppressing transmission and limiting the virus' substantial public health, economic and societal burden," added Professor Crisanti.

As well as identifying the proportion of asymptomatic cases, the team also found that asymptomatic people had a similar 'viral load' - the total amount of virus a person has inside them - as symptomatic patients.

Viral load also appeared to decrease in people who had no symptoms to begin with but later developed symptoms, suggesting that asymptomatic and pre-symptomatic transmission could contribute significantly to the spread of disease, making testing and isolating even more important in controlling outbreaks.

Co-lead researcher Dr Ilaria Dorigatti, from the MRC Centre for Global Infectious Disease Analysis, Jameel Institute (J-IDEA), at Imperial College London, said: "The Vò study demonstrates that the early identification of infection clusters and the timely isolation of symptomatic as well as asymptomatic infections can suppress transmission and curb an epidemic in its early phase. This is particularly relevant today, given the current risk of new infection clusters and of a second wave of transmission.

"There are still many open questions about the transmission of the SARS-CoV-2 virus, such as the role of children and the contribution of asymptomatic carriers to transmission. Finding answers to these questions is crucial to identifying targeted and sustainable control strategies to combat the spread of SARS-CoV-2 in Italy and around the world."

Professor Enrico Lavezzo, from the Department of Molecular Medicine at the University of Padua said: "The result concerning asymptomatic carriers is key. We took a picture of the Vò population and found that about half of the population testing positive had no symptoms at the time of testing and some of them developed symptoms in the following days. This tells us that if we find a certain number of symptomatic people testing positive, we expect the same number of asymptomatic carriers that are much more difficult to identify and isolate.

"The fact that the viral load is comparable between symptomatic and asymptomatic carriers means even asymptomatic infections have the potential to contribute to transmission, as some of the reconstructed chain of transmission obtained from the detailed contact tracing conducted in Vò confirmed.

"On the one hand, it is likely that a symptomatic infection transmits large quantities of virus, for example via coughing, but it is also reasonable to think that symptoms may induce a person with a symptomatic infection to stay at home, limiting the number of contacts and hence the transmission potential. On the other hand, someone with an asymptomatic infection is entirely unconscious of carrying the virus and, according to their lifestyle and occupation, could meet a large number of people without modifying their behaviour."

Enrico Lavezzo, Elisa Franchin, Constanze Ciavarella, Gina Cuomo-Dannenburg, Luisa Barzon, Claudia Del Vecchio, Lucia Rossi, Riccardo Manganelli, Arianna Loregian, Nicolò Navarin, Davide Abate, Manuela Sciro, Stefano Merigliano, Ettore De Canale, Maria Cristina Vanuzzo, Valeria Besutti, Francesca Saluzzo, Francesco Onelia, Monia Pacenti, Saverio Parisi, Giovanni Carretta, Daniele Donato, Luciano Flor, Silvia Cocchio, Giulia Masi, Alessandro Sperduti, Lorenzo Cattarino, Renato Salvador, Michele Nicoletti, Federico Caldart, Gioele Castelli, Eleonora Nieddu, Beatrice Labella, Ludovico Fava, Matteo Drigo, Katy AM Gaythorpe, Imperial College COVID-19 Response Team, Alessandra R Brazzale, Stefano Toppo, Marta Trevisan, Vincenzo Baldo, Christl A Donnelly, Neil M Ferguson, Ilaria Dorigatti, Andrea Crisanti.
Suppression of a SARS-CoV-2 outbreak in the Italian municipality of Vo'.
Nature, 2020. doi: 10.1038/s41586-020-2488-1

Most Popular Now

How SARS-CoV-2 mutates to escape antibody binding

In a recurring pattern of evolution, SARS-CoV-2 evades immune responses by selectively deleting small bits of its genetic sequence, according to new research from the Uni...

Anticancer drug may improve outcome for severe COV…

Treating severe COVID-19 patients with the anticancer drug bevacizumab may reduce mortality and speed up recovery, according to a small clinical study in Italy and China ...

One dose of COVID-19 vaccine provokes strong immun…

Although clinical trial data are encouraging, real-world evidence with regard to the COVID-19 vaccine remains scarce. In particular, response to the vaccine among those p...

Pfizer and BioNTech commence global clinical trial…

Pfizer Inc. (NYSE: PFE) and BioNTech SE (Nasdaq: BNTX) announced today that the first participants have been dosed in a global Phase 2/3 study to further evaluate the saf...

Johnson & Johnson announces submission of appl…

Johnson & Johnson (NYSE: JNJ) (the Company) announced that Janssen Biotech, Inc., has submitted an application to the U.S. Food and Drug Administration (FDA) requesting E...

Could a nasal spray prevent coronavirus transmissi…

A nasal antiviral created by researchers at Columbia University Vagelos College of Physicians and Surgeons blocked transmission of SARS-CoV-2 in ferrets, suggesting the n...

European Commission purchases additional 150 milli…

Moderna, Inc. (Nasdaq: MRNA), a biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, today announced that the European Commission purchased an...

GSK and Vir Biotechnology expand coronavirus colla…

GlaxoSmithKline plc (LSE/NYSE: GSK) and Vir Biotechnology, Inc. (Nasdaq: VIR) have signed a binding agreement to expand their existing collaboration to include the resear...

Neandertal gene variants both increase and decreas…

Last year, researchers at Karolinska Institutet in Sweden and the Max Planck Institute for Evolutionary Anthropology in Leipzig, Germany showed that a major genetic risk ...

CureVac initiates rolling submission with European…

CureVac N.V. (Nasdaq: CVAC), a global biopharmaceutical company developing a new class of transformative medicines based on messenger ribonucleic acid (mRNA), today annou...

Pfizer and BioNTech publish data from in vitro stu…

Pfizer Inc. (NYSE: PFE) and BioNTech SE (Nasdaq: BNTX) today announced the publication in Nature Medicine of data from in vitro studies that demonstrate that sera from in...

Sinovac receives conditional marketing authorizati…

Sinovac Biotech Ltd. (NASDAQ:SVA) ("Sinovac" or the "Company"), a leading provider of biopharmaceutical products in China, announced that the China National Medical Produ...