Abou Jaoude, GJ

Correa, A

Kerr, CC

Panovska-Griffiths, J

English

UCL Discovery

Access thebmj.com - How much is covid-19 spreading via asymptomaticversus symptomatic infections?As we look at exit strategies from lockdown, these authors discuss how we canmeasure the spread of covid-19 and whether mathematical modelling helpsThe covid-19 pandemic, caused by the SARS-CoV-2 virus, continues to spreadworldwide [1]. To slow down the spread of the disease, flatten the epidemiccurve and minimise morbidity and mortality due to the pandemic,governments across the world have enacted physical distancing measures.However, as countries across the globe begin plans to relax these measures, itis important to assess whether the phasing out of physical distancingmeasures and resumption of social mixing will lead the number of infectionsto increase again with a secondary covid-19 pandemic wave.In the absence of immunisation and proactive testing strategies, a largeportion of the population may remain susceptible to infection and at risk ofexposure. To predict how the epidemic curve will behave when restrictions arelifted, it is crucial to gain a better understanding of the extent to which thevirus is spreading asymptomatically as well as symptomatically, as recentstudies from Italy [2] and China [3] have suggested.There is mixed evidence on the proportion of cases that are asymptomatic. Ascoping review suggests that between 5% and 80% of people with covid-19experience mild or asymptomatic disease, with WHO suggesting that 80% ofinfections show mild symptoms, 15% exhibit severe symptoms, and 5% fallcritically ill [1,4,5]. This implies that symptom-based control strategies areunlikely to be sufficient unless asymptomatic cases are significantly lessinfectious than symptomatic ones. New evidence from the Italian city of Vo’ atthe epicenter of the pandemic and from China indicates that the largemajority of coronavirus infections do not result in symptoms, up to 75% and80% respectively. [2,3] However, findings of other studies have suggested thatthe proportion of covid-19 cases that are asymptomatic is smaller: 10%among children, 18% among passengers on the Diamond Princess cruise shipand 42% among Japanese people evacuated from Wuhan. [6,7,8] Moreover,these studies typically have happened only at single points in time; otherstudies that have included later follow-up have shown that a significantproportion of people without symptoms upon first positive test later go on todevelop symptoms. [9]Although new information and findings are released daily on covid-19, thepredominant focus has been on people who have shown symptoms, soughthospital care, had a test, and tested positive. Therefore, the reported numberof cases does not include people that have asymptomatic infections, or thosethat have shown symptoms but self-isolated and did not seek care or testing.Consequently, we only know a fraction of the total covid-19 infections, andthus we do not know what proportion of covid-19 infections are symptomaticversus asymptomatic. This is different to previous epidemics, such as SevereAcute Respiratory Syndrome (SARS), where most of the infections weresymptomatic and could be contact traced. [10] Widespread antibody testing will tell us if people have had covid-19 and cantherefore enable a better approximation of the total number of infections –which includes both asymptomatic and symptomatic cases. This will be key toinform effective decisions and plans to lift physical distancing measures. Forexample, if widespread antibody testing suggests that a large proportion of thepopulation has already contracted covid-19, there is a smaller chance ofasymptomatic and undiagnosed cases spreading the infection oncerestrictions are eased. On the other hand, if only a small proportion of thepopulation has had the infection, then the lifting of physical distancingmeasures may have to be delayed until a vaccine, or potentially highlyeffective testing protocols and contact tracing strategies, become widelyavailable. There is therefore urgency around developing and rolling out antibody testingin the UK and worldwide. This has to be part of a continued strategy of testing,contact tracing, and isolation of infected people as the first step to relaxphysical distancing measures, once we are assured that the pandemic hasbeen sufficiently suppressed. This is in alignment with the six point strategy torelax covid-19 restrictions recommended by the WHO recently [11]. Can mathematical modelling help?Since the onset of this pandemic, mathematical modelling has been at theheart of informing decision making on mitigation and containment measures.For example, the enforcement of physical distancing measures has beenattributed to the predicted outcomes from a mathematical model of a largenumber of deaths in the absence of such measures. [12] So what canmathematical modelling tell us about the proportion of asymptomatic andsymptomatic infections that would be useful when we come out of isolation?Mathematical modelling allows us to develop a framework to mimic realityusing formulaic expressions and parameters based on what we know aboutthe spread of the virus. The model can be refined (or calibrated) to replicateknown aspects such as the number of reported infections and deaths due tocovid-19. Then, with the model calibrated to data from the onset of thepandemic to the present day, it can be used to investigate various scenariosand predict likely trends. A classic example of mathematical models used for infectious disease spreadare SEIR models. These models track populations that are susceptible (S),exposed (E), infected (I), and that have recovered from the virus (R). Theinfected population group (I) can be split into asymptomatic and symptomaticpopulations, which can be modelled separately. In this case, the model issimply known as SEIIR, in other words it has two separate infected populationgroups or model “compartments.” Such a model can project the epidemic curve for the population that isinfected and symptomatic, but also the epidemic curve for the population thatis infected and asymptomatic. By calibrating the model based on what wealready know—the epidemic curve of symptomatic infections and deathsfrom the pandemic onset to the present day—we can then predict the shapeand behaviour of the epidemic curve for the population that is infected butasymptomatic. Past studies on potential pandemic influenza outbreaks in the UK haveinvestigated scenarios similar to the physical distancing measures currentlyadopted, and estimated a substantial negative shock on the economy with aloss of around 5% of GDP [13-14]. Modelling asymptomatic cases is thereforekey as governments will find that prolonged physical distancing iseconomically and socially unsustainable. It is therefore crucial to understandhow and when the physical distancing measures can be eased, while stillensuring that mortality due to covid-19 does not increase. Morbidity andmortality are not necessarily a fixed proportion of infections if health systemcapacity is effectively expanded to cope with a predicted pandemic spread,and predictions on the behaviour of the epidemic curve post-physicaldistancing can be generated using mathematical modelling.Unfortunately, as the wide range of estimates listed above indicate, currentlythe greatest challenge to modelling asymptomatic cases is the largeuncertainty in key model parameters. It is a common saying amongmathematical modellers that “mathematical models are as good as the datathey use”.  Data based only on new infections tested positive in the context oflimited testing capacities, hospitalisations and deaths—all of which have largeconfounders and possible delay in reporting rates—are not sufficient toresolve the question of symptomatic versus asymptomatic transmission. Toresolve this question, let us hope we start widespread antibody testing andcontact tracing as soon as possible. J.Panovska-Griffiths, Senior Research Fellow and and Lecturer inMathematical modelling at UCL and Lecturer in Applied Mathematics at TheQueen’s College, Oxford University. G.J. Abou Jaoude, Institute for Global Health, University College London. A. Correa, Institute for Global Health, University College London; Section ofClinical Medicine, University of Surrey.C.C.Kerr, Institute for Disease Modeling, Bellevue, Washington; School ofPhysics, University of Sydney, Sydney, Australia.Competing interests: None declared.References:1. World Health Organization Coronavirus disease 2019 (COVID-19)Situation report -98, https://www.who.int/docs/default-source/coronaviruse/situation-reports/20200427-sitrep-98-covid-19.pdf?sfvrsn=90323472_4m, assessed 28/04/2020.2. E. Lavezzo, Franchin E, Ciavarella C, et al. Suppression of COVID-19outbreak in the municipality of Vo’, Italy. Preprint assessed on28/04/2020 and available herehttps://www.medrxiv.org/content/10.1101/2020.04.17.20053157v1.full.pdf3. Covid-19: four fifths of cases are asymptomatic, China figures indicate.BMJ2020;369:m1375 doi: https://doi.org/10.1136/bmj.m13754. COVID-19: What proportion are asymptomatic? Centre for Evidence-Based Medicine, University of Oxford, https://www.cebm.net/covid-19/covid-19-what-proportion-are-asymptomatic/, assessed28/04/2020.5. D. Thomas-Rüddel, J. Winning, P. Dickmann,D. Ouart, A. Kortgen, U.Janssens and M. Bauer.Coronavirus disease 2019 (COVID-19): update foranesthesiologists and intensivists March 2020. Anaesthesist. 2020 Mar24 : 1–10. doi: 10.1007/s00101-020-00760-36. Clinical and epidemiological features of 36 children with coronavirusdisease 2019 (COVID-19) in Zhejiang, China: an observational cohortstudy, Lancet Inf Dis, doi:10.1016/S1473-3099(20)30198-5 (epubahead of print).7. K.Mizumoto, K.Kagaya, A.Zarebski, G.Chowell.G. Estimating theasymptomatic proportion of coronavirus disease 2019 (COVID-19) caseson board the Diamond Princess cruise ship, Yokohama, Japan,2020. EuroSurveill.2020;25(10):pii=2000180. https://doi.org/10.2807/1560-7917.ES.2020.25.10.20001808. 8.H.Nishiura, T.Kobayashi, T.Miyama, A.Suzuki, et al.Estimation of theasymptomatic ratio of novel coronavirus infections (COVID-19). Preprintassessed 28th April 2020 and available here doi:https://doi.org/10.1101/2020.02.03.20020248.9. 9.Centres for Disease Control and Prevention report, Asymptomatic andPresymptomatic SARS-CoV-2 Infections in Residents of a Long-TermCare Skilled Nursing Facility — King County, Washington, March 2020,https://www.cdc.gov/mmwr/volumes/69/wr/mm6913e1.htm,assessed 28/04/202010. A. Wilder-Smith,MD. Teleman MD, BH.Heng, A.Earnest, AE. Ling,YS. LeoYS. Asymptomatic SARS coronavirus infection among healthcareworkers, Singapore. Emerg Infect Dis. 2005; 11: 1142-114511. WHO Director-General’s opening remarks at the media briefing onCOVID-19 – 13 April 2020,https://www.who.int/dg/speeches/detail/who-director-general-s-opening-remarks-at-the-media-briefing-on-covid-19–13-april-2020,assessed 28/04/2020.12. Ferguson NM, Laydon D, Nedjati-Gilani D, et al. Impact of non-pharmaceutical interventions (NPIs) to reduce COVID- 19 mortality andhealthcare demand. Preprint assessed 26th March 2020 and available athttps://www.imperial.ac.uk/media/imperial-college/medicine/sph/ide/gida-fellowships/Imperial-College-COVID19-NPI-modelling-16-03-2020.pdf.13. R.D.Smith, MR Keogh-Brown, T.Barnett. Estimating the economic impactof pandemic influenza: An application of the computable generalequilibrium model to the UK. Social Science & Medicine,2011,73(2),235-244.https://doi.org/10.1016/j.socscimed.2011.05.02514. RD.Smith, MR Keogh-Brown, T.Barnett, J.Tait. The economy-wide impactof pandemic influenza on the UK: a computable general equilibriummodelling experimentBMJ2009; 339doi: https://doi.org/10.1136/bmj.b4571 ñò

How much is covid-19 spreading via asymptomatic versus symptomatic infections?

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How much is covid-19 spreading via asymptomatic versus symptomatic infections?

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