As the far-reaching impacts of the coronavirus disease 2019 (COVID-19) pandemic expand
to more and more countries, key questions about transmission dynamics and optimal
intervention strategies remain unanswered. In particular, the age profile of susceptibility
and infectivity, the frequency of super-spreading events, the amount of transmission
in the household, and the contribution of asymptomatic individuals to transmission
remain debated. The study by Qifang Bi and colleagues
1
in The Lancet Infectious Diseases explores some of these questions by analysing detailed
contact tracing data from Shenzhen, a large and affluent city in southern China at
the border with Hong Kong. To dissect the drivers of severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) transmission, the authors modelled PCR-confirmed infections
in 391 cases and 1286 of their close contacts from Jan 14 to Feb 12, 2020.
1
Shenzhen is an interesting location to study the dynamics of SARS-CoV-2 because it
was affected early in the pandemic and reacted quickly.
2
Strict case isolation, contact tracing, and social distancing measures kept the transmission
rate near the epidemic threshold throughout the study period.
2
Bi and colleagues report that most secondary infections occurred in the household
(77 of 81), with a secondary attack rate estimated at 11·2% (95% CI 9·1–13·8) among
household contacts.
1
This figure should be considered an underestimate of the unmitigated household attack
rate of SARS-CoV-2, since transmission chains were cut short in Shenzhen because of
strict control measures. Index cases detected by symptom-based surveillance were isolated
outside of the home on average 4·6 days (95% CI 4·1–5·0) after symptom onset. Furthermore,
individuals identified via contact tracing were isolated or quarantined outside of
the home on average 2·7 days (95% CI 2·1–3·3) after symptom onset.
1
Consequently, the serial interval of SARS-CoV-2 in Shenzhen (mean estimate 6·3 days;
95% CI 5·2–7·6) should be considered a lower bound and would probably increase in
less successfully controlled outbreaks.
The age profile of PCR-confirmed infections in Shenzhen indicates that children are
as susceptible to SARS-CoV-2 infection as adults, although they are less likely to
display symptoms.
1
The distinctive age profile of COVID-19 severity has been noted very early on in the
pandemic,
3
although the biological mechanisms at play remain unclear. In the Shenzhen data, the
authors noted no difference in the transmission potential of SARS-CoV-2 from children
or adults.
1
This is in contrast to pandemic influenza virus, which is more easily transmitted
by children. It will be useful to confirm the age profile of SARS-CoV-2 transmissibility
with data from other locations and serological surveys, which capture more infections
than PCR. Age-specific susceptibility, infectivity, and severity are important factors
to get right to project the impact of school closures on SARS-CoV-2 dynamics and disease
burden. School closures exert a substantial economic toll on societies and maintaining
these interventions for long periods of time requires robust supportive evidence.
As would be expected from a well controlled outbreak, the mean R in Shenzhen was very
low, at 0·4,
1
substantially reduced from a baseline non-intervention value of 2·0–4·0.
4
This aligns with the strict interventions implemented in this city. However, the mean
R does not tell the full story. There is evidence of transmission heterogeneity with
SARS-CoV-2, with 10% of cases accounting for 90% of transmission.
1
Such a high level of heterogeneity is consistent with, if a little more extreme than,
that of SARS-coronavirus (SARS-CoV), and more pronounced than for other directly transmitted
respiratory viruses such as measles or influenza.
5
Beyond the intensity of contacts, there is no clear factor in the Shenzhen data that
could explain the high transmission potential of some infections. Further research
into the biological (eg, shedding and symptoms) and social factors (eg, type of contacts
and environment) that drive transmission heterogeneity is warranted to guide more
targeted interventions against SARS-CoV-2.
Armed with their descriptive findings, Bi and colleagues go on to simulate the impact
of case isolation and contact tracing on SARS-CoV-2 dynamics.
1
They consider a range of possible durations for the infectious period of SARS-CoV-2,
which is reasonable given the scarcity of data on this figure. They show that for
a given R, the longer the infectious period, the more easily the epidemic can be brought
under control with case-based interventions. This is because case isolation reduces
the full transmission potential of each case, particularly if the infectious period
is long and cases can be isolated 2–5 days after symptom onset. Furthermore, Bi and
colleagues show that contact-based interventions are more efficient than case-based
interventions to reduce transmission, since infected contacts are typically isolated
earlier in their infection history than index cases. This worthwhile modelling exercise
highlights the urgent need for more information about the infectious period of SARS-CoV-2.
However, there is an important caveat in this modelling work: the potential for pre-symptomatic
and asymptomatic transmission is not considered. As a result, the conclusion that
case-based or contact-based interventions alone could bring the epidemic under control
for longer durations of the infectious period is optimistic, and contrasts with previous
simulation studies.
6
Viral shedding studies and epidemiological investigations suggest that in the household,
around 40% of transmission occurs before symptom onset, the live virus is shed for
at least 1 week after symptom onset, and there is high shedding in asymptomatic individuals.7,
8, 9 Crucially, the effectiveness of case isolation and contact tracing will depend
on the fraction of transmission originating from asymptomatic and pre-symptomatic
individuals.
9
As we look towards post-lockdown strategies, we should examine the experience of countries
that have successfully controlled SARS-CoV2 transmission or have low mortality (eg,
China, Singapore, Taiwan, South Korea, Germany, and Iceland). Successful strategies
include ample testing and contact tracing, supplemented by moderate forms of social
distancing.
10
Contact tracing on the scale that is needed for the SARS-CoV-2 response is labour
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.
9
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.
9
© 2020 Flickr - Jay Sterling Austin
2020
Since January 2020 Elsevier has created a COVID-19 resource centre with free information
in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre
is hosted on Elsevier Connect, the company's public news and information website.
Elsevier hereby grants permission to make all its COVID-19-related research that is
available on the COVID-19 resource centre - including this research content - immediately
available in PubMed Central and other publicly funded repositories, such as the WHO
COVID database with rights for unrestricted research re-use and analyses in any form
or by any means with acknowledgement of the original source. These permissions are
granted for free by Elsevier for as long as the COVID-19 resource centre remains active.