Case introductions in the context of SARS-CoV-2 infections

4 January 2023

Julien Arino (Julien.Arino@umanitoba.ca)

Department of Mathematics & Data Science Nexus
University of Manitoba*

Canadian Centre for Disease Modelling (CCDM/CCMM)
NSERC-PHAC EID Modelling Consortium (CANMOD, MfPH, OMNI/RÉUNIS)

*The University of Manitoba campuses are located on original lands of Anishinaabeg, Cree, Oji-Cree, Dakota and Dene peoples, and on the homeland of the Métis Nation.
We respect the Treaties that were made on these territories, we acknowledge the harms and mistakes of the past, and we dedicate ourselves to move forward in partnership with Indigenous communities in a spirit of reconciliation and collaboration.

Thanks ..

Collaborators

  • Nicolas Bajeux
  • Pierre-Yves Boëlle (IPLESP, Sorbonne Université)
  • Amy Hurford (Memorial University of Newfoundland)
  • Evan Milliken (University of Louisville, Kentucky, USA)
  • Stéphanie Portet (University of Manitoba)
  • James Watmough (University of New Brunswick)

Funders

  • Natural Science and Engineering Council Canada (NSERC), Canadian Institutes for Health Research (CIHR) & University of Manitoba Faculty of Science Research Chairs program
  • (& logistical support) Public Health Agency of Canada (PHAC)

Outline

  1. Side note : health in Canada
  2. Human habitat fragmentation, mobility & spread of infectious diseases
  3. The first wave of COVID-19
  4. Case introductions/importations
  5. Modelling introductions
  6. Spread of SARS-CoV-2 variants
  7. Measures to control spatial spread
    a. Role of transport restrictions
    b. Role of quarantine
  8. Lessons learned and key knowledge gaps

Pathogens have been mobile for a while

It first began, it is said, in the parts of Ethiopia above Egypt, and thence descended into Egypt and Libya and into most of the King's country [Persia]. Suddenly falling upon Athens, it first attacked the population in Piraeus [..] and afterwards appeared in the upper city, when the deaths became much more frequent.

Thucydides (c. 460 BCE - c. 395 BCE)

History of the Peloponnesian War

Side note : health in Canada

Shared responsibility between federal government (F) and provinces/territories (P/T)

  • F (PHAC, Health Canada, DND): First Nations on Reserves, Armed Forces, Federal prisonners; control of entry into national territory

    • F regulate flows RoW CAN (federal quarantine, post-entry PCR), authorise vaccines, purchase vaccines then distribute to P/T based on population ( special groups)

  • P/T: everything except special groups; control of entry onto P/T territory; enforcement of laws and bylaws (except when local PF are present)

    • P/T regulate flows intra- and inter-P/T (P/T quarantine, geographic exclusions - "no travel north of 53" in CAN-MB, pre-entry quarantine for CAN-NU), nature of NPI response, vaccine roll-out

Human habitat fragmentation, mobility
&
spread of infectious diseases

JA. Spatio-temporal spread of infectious pathogens of humans. Infectious Disease Modelling (2017)

Mobility is complicated but determinant in disease spatialisation

  • Multiple modalities: foot, bicycle, personal vehicle, bus, train, boat, airplane
  • Various durations: trip to the corner shop commuting multi-day trip for work or leisure relocation, immigration or refuge seeking
  • Volumes are hard to fathom

And yet mobility drives spatio-temporal spread:

  • Black Death 1347-1353 arrived in Europe and spread following trade routes
  • SARS-CoV-1 spread out of HKG following the GATN
  • Khan, Arino, Hu et al, Spread of a novel influenza A (H1N1) virus via global airline transportation, New England Journal of Medicine (2009)

The human world is fragmented not only because of geography

  • Political divisions (jurisdictions): nation groups (e.g., EU), nations, provinces/states, regions, counties, cities..
  • Travel between jurisdictions can be complicated or impossible
  • Data is integrated at the jurisdicional level
  • Policy is decided at the jurisdictional level

Long range mobility is a bottomtoptopbottom process

The first wave of COVID-19

Amplification in Wuhan (Hubei province)

  • Details of emergence and precise timeline before amplification started unknown
  • Amplification in Wuhan
    • Cluster of pneumonia cases mostly related to the Huanan Seafood Market
    • 27 December 2019: first report to local government
    • 31 December 2019: publication
    • 8 January 2020: identification of SARS-CoV-2 as causative agent
  • 23 January 2020: lockdown Wuhan and Hubei province + face mask mandates

By 29 January, virus was found in all provinces of mainland China

First detections outside China

Date Location Note
13 Jan. Thailand Arrived 8 Jan.
16 Jan. Japan Arrived 6 Jan.
20 Jan. Republic of Korea Airport detected on 19 Jan.
20 Jan. USA Arrived Jan. 15
23 Jan. Nepal Arrived 13 Jan.
23 Jan. Singapore Arrived 20 Jan.
24 Jan. France Arrived 22 Jan.
24 Jan. Vietnam Arrived 13 Jan.
25 Jan. Australia Arrived 19 Jan.
25 Jan. Malaysia Arrived 24 Jan.

Caveat : evidence of earlier spread

  • Report to Wuhan authorities on 27 December 2019
  • First export detections in Thailand and Japan on 13 and 16 January 2020 (with actual importations on 8 and 6 January)

amplification must have been occuring for a while longer

  • France: sample taken from 42-year-old male (last foreign travel to Algeria in August 2019) who presented to ICU on 27 December 2019
  • Retrospective studies in United Kingdom and Italy also showed undetected COVID-19 cases in prepandemic period

Untangling the first case issue

  • Robert, Rossman & Jaric. Dating first cases of COVID-19. PLoS Pathogens (2021). Find likely timing of first case of COVID-19 in China as November 17 (95% CI October 4)
  • Pekar, Worobey, Moshiri, Scheffler & Wertheim. Timing the SARS-CoV-2 index case in Hubei province. Science (2021). Period between mid-October and mid-November 2019 is plausible interval when the first case of SARS-CoV-2 emerged in Hubei province.

Important when trying to understand global spread, so let me illustrate with the model I used, taking into account model evolution since

Back-calculating the start of spread (example of China)

Cumulative confirmed case counts in China as reported to WHO was cases on

Let be a point in parameter space. Solve ODE numerically over , with the population of China, and other state variables 0. This gives a solution . Extracting from this solution, obtain cumulative number of new detections as

Let be s.t. ; then

  • For SARS-CoV-1 (2003), the point of introduction on the GATN is known with certainty (Metropole Hotel, HKG, 2003-02-21)
  • For SARS-CoV-2, uncertainty remains and will probably never be lifted

Transmission within national jurisdictions was heterogeneous

Moving from ISO-3166-3 (nation or territory) level to smaller sub-national jurisdictions, the picture is more contrasted

Next slide: Example of activation of North American health regions/municipios/counties

Case introductions/importations

Introductions/Importations

  • In Ecology, importations are called introductions and have been studied for a while, because they are one of the drivers of evolution and, more recently, because of invasive species

  • An importation occurs when an individual who acquired the infection in a jurisdiction makes their way to another jurisdiction while still infected with the disease

  • Geographies greatly influence reasoning

    • At the country level, importations quickly become less relevant
    • Consider an isolated location of 500 people.. disease may become extinct then be reimported

Modelling introductions

The spread process in a jurisdiction-based world

Spread of SARS-CoV-2 variants

Understanding variant dynamics and how to control it

  • Suppose a resident variant is propagating in a population, say, the original wild type or, now, B.1.1.7
  • A novel variant comes along, say B.1.617.2 (SARS-CoV-2 Delta) that is more transmissible

Q:

  • How long until novel replaces resident variant in terms of propagation?
  • What role do importations play in this?
  • How does one diminish role of importations and how useful are measures used to do so?

Measures to control spatial spread

Almost exclusively attacked from the perspective of would-be importer

In practice:

  • Travel restrictions/interruptions
  • Quarantine

Role of travel restrictions

Mur de la Peste in Cabrières-d’Avignon

Interruption of travel for COVID-19

Country Date travel suspension Date first case
Seychelles 2020-03-03 2020-03-14
El Salvador 2020-03-17 2020-03-18
Cape Verde 2020-03-17 2020-03-20
Sudan 2020-03-17 2020-04-05
Marshall Islands 2020-04-22 2020-10-29
Vanuatu 2020-03-20 2020-11-11
North Korea 2020-01-21 Unreported
Turkmenistan 2020-03-20 Unreported
Tuvalu 2020-03-26 2022-05-20 (potentially earlier on 2021-11-02)

Untangling the contribution of introduced cases

Time and time again (e.g., right now with China), top jurisdictional level PH authorities take travel interruption measures

What is really the contribution of introductions to overall spread within a jurisdiction?

Consider an importation layer separating introduced (imported) cases from locally generated ones

Introductions in a metapopulation model
Left: low movement rate. Right: higher movement rate

Effect of quarantine

Quarantine Isolation

  • Quarantine is indiscriminate and applies to all incoming flux
  • Isolation is imposed to known or suspected cases and known contacts
  • First used in (the lazzarettos of) Dubrovnik in 1377
  • Name comes from Venitian quarantena
Lazzaretto vecchio

Effect of quarantine on importation rates

the mean time between case importations, the mean quarantine-regulated time between case importations, the efficacy of quarantine (in %). Then

Suppose 5 days and efficacy of quarantine is 90% at 7 days and 98% at 14 days, respectively

Then 50 and 250 days, respectively

Lessons learned
&
key questions/knowledge gaps

Lessons learned

  • Airport screening sometimes worked to detect the first imports
  • Travel interruptions work .. sometimes (e.g., ISL, NZL, CAN-NL)
  • Travel interruptions often do not work (e.g., world very few)
  • Governments like travel interruptions regardless:

a powerful expression of state's sovereignty, immigration control provides a typical avenue for governments to reassure their citizens and bolster a national sense of belonging, while providing an ideal scapegoat for their own failure or negligence [Chetail (2020)]

  • Quarantine seems to work quite well but needs to be applied homogeneously

Key questions/knowledge gaps

  • Space is a fundamental component of the epidemic spread process and cannot be ignored, both in modelling and in public health decision making
  • How to apprehend/model the absolutely colossal amount of mobility taking place and the not less consequent variety of transport modalities and purposes
  • How to get governments to understand that a pandemic is a global phenomenon with local "phenotypes", so uncoordinated unilateral travel policies have virtually no chance of success (treat the symtoms, not the cause)
  • What are the necessary conditions for travel interruptions to work?
  • Because of scapegoating, the borders were closed in theory. However, because of .. real life, they were not in practice. How closed is closed?

Arrival into CAN from 2020-04-01 to 2021-03-31

(border was "closed")

Traveller characteristics Total
Total non-resident travellers 1,491,233
Total Canadian residents 3,653,592
Total other travellers 5,963,285
Total international travellers 11,108,110

80/100K/day on average (678/100K/day 2019-04 2020-03)

Emergency response during public health crises

  • Get in this to help .. and for the adrenalin
  • Get out of this burned out (20 hours a day 7 days a week the first 2-3 months, down to 80-100 hours/week for a year and a half more, now there are weeks when I don't even do 20 hours of COVID)
  • Interesting and frustrating at the same time
    • You are 1 of many being consulted. Don't expect anything you say to be used
    • Expect wild goose chases, many aborted publications (it's not relevant anymore!)
    • You sometimes get insider information and data but are usually sworn to secrecy (data is given to you so you can help decide, not so you can garnish your publication list)

CMPD 6 - Winnipeg 22 to 26 May 2023

Computational and Mathematical Population Dynamics

(Fort Lauderdale 2019, Taiyuan 2013, Bordeaux 2010, Campinas 2007, Trento 2004)

Follows MPD: University of Mississippi 1986, Rutgers University 1989, Pau 1992, Rice University 1995, Zakopane 1998, Trento 2004

And DeStoBio: Sofia 1997, Purdue 2000, Trento 2004

See information on https://cmpd6.github.io/

Merci / Miigwech / Thank you

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