The value of early transmission dynamic studies in emerging infectious diseases
Authors: Emma McBryde
Journal: The Lancet Infectious Diseases (2020)

The world is braced for a public health emergency of international concern caused by a novel emerging infectious disease, a coronavirus with similarities to severe acute respiratory syndrome coronavirus (SARS-CoV). Person-to-person transmission of SARS-CoV-2, the causative agent of coronavirus disease 2019 (COVID-19), started in December, 2019, in Wuhan, China and has spread to become a global pandemic, with, as of Feb 26, 2020, community transmission in Italy, Iran, and South Korea. Modelling studies have aided understanding of COVID-19 dynamics from the first announcement of the epidemic and publication of the genetic sequence of the causative virus. Initial phylogenetic analysis of closely related viruses suggested highly linked person-to-person spread of SARS-CoV-2 originating from mid-November to early December, 2019.1Lu R Zhao X Li J et al.Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding.Lancet. 2020; 395: 565-574Summary Full Text Full Text PDF PubMed Scopus (7798) Google Scholar, 2GISAID: Genomic epidemiology of BetaCoV 2019–2020.https://www.gisaid.org/epiflu-applications/next-sars-cov2-app/Google Scholar Following this, modellers provided simple calculations that identified a mismatch between reported cases in China and reported importations of cases from travellers. Based on travel volumes, modellers inferred3Rothe C Schunk M Sothmann P et al.Transmission of 2019-nCoV infection from an asymptomatic contact in Germany.N Engl J Med. 2020; (published online Jan 30.)DOI:10.1056/NEJMc2001468Crossref PubMed Scopus (2726) Google Scholar that cases in Wuhan were underestimated by a factor of 40—a crucially important finding. Further calculations, again based on travel volumes, suggested that some countries would be expected to have many more travel-related cases than had been notified,4De Salazar PM Niehus R Taylor A Buckee CO Lipsitch M Using predicted imports of 2019-nCoV cases to determine locations that may not be identifying all imported cases.medRxiv. 2020; (published online Feb 11.) (preprint).DOI:10.1101/2020.02.04.20020495Google Scholar drawing attention to the possibility of undetected cases and community transmission in several countries. Transmission dynamic models are a necessary first step in understanding the pandemic potential of an emerging infectious disease, including estimating the reproduction number—the number of new cases arising from a typical infected case. The first published transmission dynamic study of COVID-19 was rapid and uncomplicated, estimating the basic reproduction number as time-invariant5Wu JT Leung K Leung GM Nowcasting and forecasting the potential domestic and international spread of the 2019-nCoV outbreak originating in Wuhan, China: a modelling study.Lancet. 2020; (published online Jan 31)https://doi.org/10.1016/S0140-6736(20)30260-9Summary Full Text Full Text PDF Scopus (2827) Google Scholar without exploring some of the major underlying assumptions, such as lack of infectiousness during the incubation period. Since this early publication, many estimates for the reproduction rate have appeared, ranging from around 2 to more than 6.6Liu Y Gayle AA Wilder-Smith A Rocklöv J The reproductive number of COVID-19 is higher compared to SARS coronavirus.J Travel Med. 2020; (published online Feb 13.)DOI:10.1093/jtm/taaa021Crossref PubMed Scopus (1892) Google Scholar In The Lancet Infectious Diseases, the study by Adam Kucharski and colleagues7Kucharski AJ Russell TW Diamond C et al.Early dynamics of transmission and control of COVID-19: a mathematical modelling study.Lancet Infect Dis. 2020; (publised online March 11)https://doi.org/10.1016/S1473-3099(20)30144-4Summary Full Text Full Text PDF PubMed Scopus (1561) Google Scholar addresses many of the assumptions of earlier works. The report contributes a time-varying reproduction number, showing the effect of the massive public health interventions put in place by China from Jan 23, 2020. By using additional datasets of travel-related exported cases, Kucharski and colleagues do not rely entirely on notified cases in Wuhan, which are likely to bias estimates caused by changes in case detection over time. The authors show that the reproduction number fell almost to the threshold value of 1 during the unprecedented public health restrictions in China.7Kucharski AJ Russell TW Diamond C et al.Early dynamics of transmission and control of COVID-19: a mathematical modelling study.Lancet Infect Dis. 2020; (publised online March 11)https://doi.org/10.1016/S1473-3099(20)30144-4Summary Full Text Full Text PDF PubMed Scopus (1561) Google Scholar Kucharski and colleagues7Kucharski AJ Russell TW Diamond C et al.Early dynamics of transmission and control of COVID-19: a mathematical modelling study.Lancet Infect Dis. 2020; (publised online March 11)https://doi.org/10.1016/S1473-3099(20)30144-4Summary Full Text Full Text PDF PubMed Scopus (1561) Google Scholar suggest that chains of transmission might not take off initially and might require up to four imported cases to establish transmission. This estimate assumes that SARS-CoV-2 has heterogeneity of infectiousness similar to SARS, which was characterised by a number of super-spreaders with most cases infecting no other people. If SARS-CoV-2 has a more homogenous infectiousness profile (to which emerging evidence is pointing) in which most people infect two to three others, the risk of established local transmission with a single imported case is considerably higher. This study answers—at least in one location over a restricted time—a critical question regarding this emerging pandemic, its reproduction number.7Kucharski AJ Russell TW Diamond C et al.Early dynamics of transmission and control of COVID-19: a mathematical modelling study.Lancet Infect Dis. 2020; (publised online March 11)https://doi.org/10.1016/S1473-3099(20)30144-4Summary Full Text Full Text PDF PubMed Scopus (1561) Google Scholar This crucial number began at 2·35 and declined to 1·05 over the course of December, 2019, and January, 2020. Many questions remain unanswered and should be addressed with urgency, including the infectiousness of cases over the duration of their illness—particularly how much transmission could occur from people who are unaware that they have illness, including asymptomatic and mildly symptomatic people. Initial reports suggest that live virus can be recovered from asymptomatic or mildly symptomatic people,3Rothe C Schunk M Sothmann P et al.Transmission of 2019-nCoV infection from an asymptomatic contact in Germany.N Engl J Med. 2020; (published online Jan 30.)DOI:10.1056/NEJMc2001468Crossref PubMed Scopus (2726) Google Scholar which is of great concern as it will make disease much harder to detect and therefore control. However, what contribution such people make to the overall epidemic is unknown. Additionally, the infection severity, including the infection-fatality rate across different ages and risk groups, must be established. Early reports provide estimates of case fatality of 2·3% within China.8WHOCoronavirus disease 2019 (COVID-19) situation report—29. Feb 19, 2020.https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200218-sitrep-29-covid-19.pdf?sfvrsn=6262de9e_2Google Scholar However, it is notoriously difficult to make such estimates early in an outbreak,9Ghani AC Donnelly CA Cox DR et al.Methods for estimating the case fatality ratio for a novel, emerging infectious disease.Am J Epidemiol. 2005; 162: 479-486Crossref PubMed Scopus (178) Google Scholar and it is clear that not all infections become cases and studies of many tiers of severity (deaths measured as a proportion of hospitalisations, notified cases and syndromic surveillance, and even potentially serosurveillance testing when available) will be needed to establish infection-fatality rates. Ongoing modelling and surveillance should continue at the epicentre of the pandemic in mainland China to assess the effect of public health measures. However, attention must also move to the emerging foci outside of China, including Italy, Iran, and South Korea, to determine if the reproduction ratio might vary in different climates and sociological contexts. New foci of infection across different continents change the risk to global communities, as this coronavirus becomes a pandemic. I declare no competing interests. Early dynamics of transmission and control of COVID-19: a mathematical modelling studyOur results show that COVID-19 transmission probably declined in Wuhan during late January, 2020, coinciding with the introduction of travel control measures. As more cases arrive in international locations with similar transmission potential to Wuhan before these control measures, it is likely many chains of transmission will fail to establish initially, but might lead to new outbreaks eventually. Full-Text PDF Open Access