Science Abc3517 Full
Science Abc3517 Full
The worldwide pandemic of SARS-CoV-2, the coronavirus We present a suite of modeling analyses to characterize
which causes COVID-19, has resulted in unprecedented re- the dynamics of SARS-CoV-2 transmission in France and the
sponses, with many affected nations confining residents to impact of the lockdown on these dynamics. We elucidate the
their homes. Much like the rest of Europe, France has been risk of SARS-CoV-2 infection and severe outcomes by age and
hit hard by the epidemic and went into lockdown on the 17 sex and estimate the current proportion of the national and
March 2020. It was hoped that this would result in a sharp regional populations that have been infected and might be at
decline in ongoing spread, as was observed when China least temporarily immune (4). These models support
locked down following the initial emergence of the virus (1, healthcare planning of the French government by capturing
2). Following the expected reduction in cases, the French gov- hospital bed capacity requirements.
ernment has announced it will ease restrictions on the 11 May As of 7 May 2020, there were 95,210 incident hospitaliza-
2020. To exit from the lockdown without escalating infec- tions due to SARS-CoV-2 reported in France and 16,386
tions, we need to understand the underlying level of popula- deaths in hospitals, with the east of the country and the cap-
tion immunity and infection, identify those most at risk for ital, Paris, particularly affected (Fig. 1, A and B). The mean
severe disease and the impact of current control efforts. age of hospitalized patients was 68ya and the mean age of the
Daily reported numbers of hospitalizations and deaths deceased was 79ya with 50.0% of hospitalizations occurring
only provide limited insight into the state of the epidemic. in individuals >70ya and 81.6% of deaths within that age
Many people will either develop no symptoms or symptoms bracket; 56.2% of hospitalizations and 60.3% of deaths were
so mild they will not be detected through healthcare-based male (Fig. 1, C to E). To reconstruct the dynamics of all infec-
surveillance. The concentration of hospitalized cases in older tions, including mild ones, we jointly analyze French hospital
individuals has led to hypotheses that there may be wide- data with the results of a detailed outbreak investigation
spread “silent” transmission in younger individuals (3). If the aboard the Diamond Princess cruise ship where all passen-
majority of the population is infected, viral transmission gers were subsequently tested (719 infections, 14 deaths cur-
would slow, potentially reducing the need for the stringent rently). By coupling the passive surveillance data from
intervention measures currently employed. French hospitals with the active surveillance performed
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aboard the Diamond Princess, we disentangle the risk of be- number of R0 = 3.0, it would require around 65% of the pop-
ing hospitalized in those infected from the underlying prob- ulation to be immune for the epidemic to be controlled by
ability of infection (5, 6). immunity alone. Our results therefore strongly suggest that,
We find that 3.6% of infected individuals are hospitalized without a vaccine, herd immunity on its own will be insuffi-
(95% CrI: 2.1–5.6), ranging from 0.2% (95% CrI: 0.1–0.2) in cient to avoid a second wave at the end of the lockdown. Ef-
females under <20ya to 45.9% (95% CrI: 27.2–70.9) in males ficient control measures need to be maintained beyond the 11
>80ya (Fig. 2A and table S1). Once hospitalized, on average May.
19.0% (95% CrI: 18.7–19.4%) patients enter ICU after a mean Our model can help inform the ongoing and future re-
delay of 1.5 days (fig. S1). We observe an increasing probabil- sponse to COVID-19. National ICU daily admissions have
ity of entering ICU with age—however, this drops for those gone from 700 at the end of March to 66 on 7 May. Hospital
>70ya (Fig. 2B and table S2). Overall, 18.1% (95% CrI: 17.8– admissions have declined from 3600 to 357 over the same
18.4) of hospitalized individuals go on to die (Fig. 2C). The time period, with consistent declines observed throughout
overall probability of death among those infected (the Infec- France (fig. S5). By 11 May we project 3900 (range: 2600–
tion Fatality Ratio, IFR) is 0.7% (95% CrI: 0.4–1.0), ranging 6300) daily infections across the country, down from between
from 0.001% in those under 20ya to 10.1% (95% CrI: 6.0–15.6) 150,000–390,000 immediately prior to the lockdown. At a re-
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dynamics may be different in these closed populations. This (COVID-19) using age-adjusted data from the outbreak on the Diamond Princess
means our estimates of immunity in the general population cruise ship, February 2020. Euro Surveill. 25, 2000256 (2020).
doi:10.2807/1560-7917.ES.2020.25.12.2000256 Medline
are unaffected by deaths in retirement homes, however, in
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transmission potential and virulence of coronavirus disease 2019 (COVID-19) in
wider community, we would underestimate the proportion of Wuhan City: China, January-February, 2020. medRxiv 2020.02.12.20022434
the population infected. Analyses of excess death will be im- [Preprint]. 13 March 2020. https://doi.org/10.1101/2020.02.12.20022434.
portant to explore these issues.
9. L. Peeples, News Feature: Avoiding pitfalls in the pursuit of a COVID-19 vaccine.
This study shows the massive impact the French lock- Proc. Natl. Acad. Sci. U.S.A. 117, 8218–8221 (2020).
down had on SARS-CoV-2 transmission. Our modeling ap- doi:10.1073/pnas.2005456117 Medline
proach has allowed us to estimate underlying probabilities of 10. D. Ricke, R. W. Malone, Medical Countermeasures Analysis of 2019-nCoV and
infection, hospitalization and death, which is essential for the Vaccine Risks for Antibody-Dependent Enhancement (ADE), 27 February 2020;
interpretation of COVID-19 surveillance data. The forecasts https://ssrn.com/abstract=3546070.
we provide can inform lockdown exit strategies. Our esti- 11. J. Yang, Y. Zheng, X. Gou, K. Pu, Z. Chen, Q. Guo, R. Ji, H. Wang, Y. Wang, Y. Zhou,
mates of a low level of immunity against SARS-CoV-2 indi- Prevalence of comorbidities and its effects in patients infected with SARS-CoV-2:
cates that efficient control measures that limit transmission A systematic review and meta-analysis. Int. J. Infect. Dis. 94, 91–95 (2020).
7. T. W. Russell, J. Hellewell, C. I. Jarvis, K. van Zandvoort, S. Abbott, R. Ratnayake, S. 20. G. Béraud, S. Kazmercziak, P. Beutels, D. Levy-Bruhl, X. Lenne, N. Mielcarek, Y.
Flasche, R. M. Eggo, W. J. Edmunds, A. J. Kucharski; Cmmid Covid-Working Yazdanpanah, P.-Y. Boëlle, N. Hens, B. Dervaux, The French connection: The first
Group, Estimating the infection and case fatality ratio for coronavirus disease large population-based contact survey in France relevant for the spread of
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infectious diseases. PLOS ONE 10, e0133203 (2015). permits unrestricted use, distribution, and reproduction in any medium,
doi:10.1371/journal.pone.0133203 Medline provided the original work is properly cited. To view a copy of this license, visit
https://creativecommons.org/licenses/by/4.0/. This license does not apply to
21. K. Mizumoto, K. Kagaya, A. Zarebski, G. Chowell, Estimating the asymptomatic figures/photos/artwork or other content included in the article that is credited
proportion of coronavirus disease 2019 (COVID-19) cases on board the Diamond to a third party; obtain authorization from the rights holder before using such
Princess cruise ship, Yokohama, Japan, 2020. Euro Surveill. 25, (2020). material.
doi:10.2807/1560-7917.ES.2020.25.10.2000180 Medline
SUPPLEMENTARY MATERIALS
22. Stan Development Team, RStan: the R interface to Stan (2020); https://mc- science.sciencemag.org/cgi/content/full/science.abc3517/DC1
stan.org/. Materials and Methods
23. Z. Du, X. Xu, Y. Wu, L. Wang, B. J. Cowling, L. A. Meyers, Serial interval of COVID- Supplementary Text
19 among publicly reported confirmed cases. Emerg. Infect. Dis. Figs. S1 to S17
10.3201/eid2606.200357 (2020). doi:10.3201/eid2606.200357 Medline Tables S1 to S12
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Fig. 1. COVID-19 hospitalizations and deaths in France. (A) Cumulative
number of general ward and ICU hospitalizations, ICU admissions and
deaths from SARS-CoV-2 in France. The green line indicates the time when
the lockdown was put in place in France. (B) Distribution of deaths in
France. Number of (C) hospitalizations, (D) ICU and (E) deaths by age group
and sex in France.
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Fig. 2. Probabilities of hospitalization, ICU admittance and death.
(A) Probability of hospitalization among those infected as a function of
age and sex. (B) Probability of ICU admission among those hospitalized
as a function of age and sex. (C) Probability of death among those
hospitalized as a function of age and sex. (D) Probability of death among
those infected as a function of age and sex. For each panel, the black line
and grey shaded region represents the overall mean across all ages. The
boxplots represent the 2.5, 25, 50, 75 and 97.5 percentiles of the
posterior distributions.
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Fig. 3. Time course of the SARS-CoV-2 epidemic to 11 May 2020. (A) Daily
admissions in ICU in metropolitan France. (B) Number of ICU beds occupied
in metropolitan France. (C) Daily hospital admissions in metropolitan
France. (D) Number of general ward beds occupied in metropolitan France
(E) Daily new infections in metropolitan France (logarithmic scale).
(F) Predicted proportion of the population infected by 11 May 2020 for each
of the 13 regions in metropolitan France. (G) Predicted proportion of the
population infected in metropolitan France. The black circles in panels (A),
(B), (C) and (D) represent hospitalization data used for the calibration and
the open circles hospitalization data that were not used for calibration. The
dotted lines in panels (E) and (G) represent the 95% uncertainty range
stemming from the uncertainty in the probability of hospitalization following
infection.
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Fig. 4. Sensitivity analyses considering different modeling assumptions.
(A) Infection fatality rate (%). (B) Estimated reproduction numbers before
(R0) and during lockdown (Rlockdown). (C) Predicted daily new infections on 11
May. (D) Predicted proportion of the population infected by 11 May. The
different scenarios correspond to: Children less inf. – Individuals <20ya are
half as infectious as adults; No Change CM – the structure of the contact
matrix is not modified by the lockdown; CM SDE – Contact matrix after
lockdown with very high social distancing of the elderly; Constant AR –
Attack rates are constant across age groups; Higher IFR – French people
25% more likely to die than Diamond Princess passengers; Higher AR DP –
25% of the infections were undetected on the Diamond Princess cruise ship;
Delay Distrib – Single hospitalization to death delay distribution; Higher
delay to hosp – 8 days on average between symptoms onset and
hospitalization for patients who will require an ICU admission and 9 days on
average between symptoms onset and hospitalization for the patients who
will not. For estimates of IFR and reproduction numbers before and during
lockdown, we report 95% credible intervals. For estimates of daily new
infections and proportion of the population infected by 11 May, we report the
95% uncertainty range stemming from the uncertainty in the probability of
hospitalization given infection.
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Estimating the burden of SARS-CoV-2 in France
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Hozé, Jehanne Richet, Claire-Lise Dubost, Yann Le Strat, Justin Lessler, Daniel Levy-Bruhl, Arnaud Fontanet, Lulla Opatowski,
Pierre-Yves Boelle and Simon Cauchemez
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REFERENCES This article cites 15 articles, 4 of which you can access for free
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