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Thursday, May 14, 2020

Testing & Intensive Contact Tracing Needed to Limit COVID-19 Spread

By Peter M. Goodwin

SHENZHEN, China—A research study has reported what could become a blueprint for driving away the coronavirus pandemic everywhere. Chinese and American researchers reported in The Lancet Infectious Diseases how a city with a population of over 12 million had largely eliminated COVID-19 transmission by mid-February 2020, with the help of widespread testing for the infection—including tracing and testing close contacts of infected persons—accompanied by strict isolation of cases identified (and also their contacts) preventing further cross-infection (2020; https://doi.org/10.1016/S1473-3099(20)30287-5).

"To our knowledge this is the first analysis of SARS-CoV-2 (COVID-19) transmission and natural history—based on a large primary dataset of cases and close contacts—for which the mode of surveillance (symptom-based vs. contact-based) was sufficiently documented and RT-PCR testing was nearly universal," wrote two of the study's co-authors, Justin Lessler, PhD, Associate Professor in the Department of Epidemiology at Johns Hopkins Bloomberg School of Public Health in Baltimore, and Tiejian Feng, M Phil, from Shenzhen Center for Disease Control and Prevention in Nanshan, Shenzhen, China.

"These results shed further light on how SARS-CoV-2 is transmitting, how severe it is, and how effective control measures can be in specific contexts. We provide a key piece of evidence supporting intensive contact tracing and highlighting that children might be an important target for interventions aimed at reducing transmission, even if they do not get sick."

Testing all close contacts made it possible for those who were infected to be identified and isolated sooner to reduce the spread of the virus. "We found that contact-based surveillance in Shenzhen reduced the duration an infected individual transmits in the community by 2 days. These findings are important for understanding the burden of COVID-19 and for strategic planning across the world," wrote Lessler and Feng.

Study Details

The Shenzhen Center for Disease Control and Prevention (Shenzhen CDC) collected data on all 391 cases of COVID-19 and 1,286 of their close contacts with the aim of tracking the epidemic beyond its origin in Hubei province. The researchers documented differences in demographics and severity between cases identified through symptom-based surveillance and their contacts. They estimated the time to key events, such as confirmation of the infection, isolation, and recovery.

Through contact tracing they were able to describe COVID-19 transmission by key factors such as the household secondary attack rate (the proportion of household members who become infected from an infected individual), the serial interval (duration between symptom onset of a primary case and symptom onset of its secondary cases) found to be 6.3 days, and the reproductive number, R (the average number of persons who become infected from a single case).

Complete Dataset

The study documented a fairly complete dataset of all COVID-19 cases and their close contacts with the aim of gaining clear information on key factors such as the incubation period of COVID-19, the proportion of infected individuals who are asymptomatic, the transmissibility of the virus, and how gender and age influence infection risk.

Widespread testing with reverse transcription polymerase chain reaction (RT-PCR) was conducted to identify infections in anybody with symptoms and their close contacts. In addition, others considered at risk were tested for active infection, including travelers from Hubei (regardless of symptoms), patients at local hospitals, and individuals who had fever.

"We present one of the first estimates of the serial interval, secondary household attack rate, and dispersion (tendency towards super spreading) for SARS-CoV-2 [COVID-19] based on active surveillance data," wrote Feng and Lessler.

Original Findings From Contact Testing

The tests on asymptomatic contacts of cases revealed that the infection rate was not significantly associated with age. The study also found that not all close contacts became infected. Within the household 11.2 percent of close contacts were infected. On average 6.6 percent of all close contacts (counting all persons with whom an infected person lived, travelled or took meals) became infected. It was also found that children younger than 10 were just as commonly infected by contact with an infected person as adults (7.4% for all types of close contacts), but were much less likely to have symptoms. "Infection rates in young children are not lower than the population average even if rates of clinical disease are," the researchers wrote.

Nearly 30 percent of all contacts found to be infected did not have a fever when they were first tested positive for COVID-19. And among infected contacts only four out of five had any symptoms at all—leaving an estimated rate of 20 percent of individuals who had "silent" (asymptomatic) infection.

Patients with symptoms were isolated and treated at hospitals chosen for this purpose, irrespective of their RT-PCR findings. Persons with asymptomatic infection were quarantined at specifically chosen locations. All close contacts with infected persons and those who had recently travelled from Hubei province were also isolated at home or at a designated facility and monitored for 14 days. They were only released from isolation after a negative RT-PCR result. The basic demographics, signs and symptoms, disease severity, and the history of any exposure to infection were recorded for all cases.

No gender bias was found in the infection rates among traced contacts who tested positive. "Any tendency for cases to be male or older (beyond the underlying population distribution) disappears," wrote the investigators. A total of 187 males and 204 females were infected with a mean age 45 years, and four out of five aged between 30 and 69.

However, men more frequently had severe symptoms than women (odds ratio 2·5). Also, the probability of having severe symptoms increased slightly with age. The rate of infection among contacts was broadly similar across all ages.

By Feb 22, 2020 three patients had died and 225 had recovered. The estimated median incubation was 4·8 days and most infected people developed symptoms within 2 weeks of infection. Median time to recovery was 20·8 days. Cases who had been detected because they had symptoms had the infection confirmed on average 5·5 days after symptom onset. But those tested because they were close contacts had their infections confirmed more than two days sooner.

The average reproductive number (R) was reduced by the mitigation measures to 0·4—well below the level of 1.0 required for the epidemic to diminish. The researchers noted that insights gained from the analysis could help with controlling the disease elsewhere and guiding the global response.

"These results paint a positive picture of the impact of heightened surveillance and isolation in Shenzhen." But the researchers warn that uncertainties about rates of asymptomatic infection "must temper any hopes of stopping the COVID-19 pandemic by these measures."

"The experience of COVID-19 in the city of Shenzhen may demonstrate the huge scale of testing and contact tracing that's needed to reduce the virus spreading," said co-author Ting Ma, PhD, from the Harbin Institute of Technology at Shenzhen, China, in a comment about the research. "Some of the strict control measures enforced here, such as isolating people outside their homes, might be unlikely to be replicated elsewhere, but we urge governments to consider our findings in the global response to COVID-19."

Comment

In a comment article, Cécile Viboud, PhD, and epidemiologist from the National Institutes of Health, wrote that she was in favor of examining the experience of countries that had successfully controlled COVID-19 transmission or had low mortality (including China, Singapore, Taiwan, South Korea, Germany, and Iceland). "Successful strategies include ample testing and contact tracing, supplemented by moderate forms of social distancing," she wrote.

"Contact tracing on the scale that is needed for the SARS-CoV-2 response is labor-intensive, and imperfect if done manually. Hence, new technology-based approaches are greatly needed to assist in identification of contacts, especially if case detection is aggressive. Building on the SARS-CoV-2 experience in Shenzhen and other settings, we contend that enhanced case finding and contact tracing should be part of the long-term response to this pandemic—this can get us most of the way towards control," wrote Viboud.

Peter M. Goodwin is a contributing writer.