Selection for infectivity profiles in slow and fast epidemics, and the rise of SARS-CoV-2 variants
- Collège de France, France
- Institut Pasteur, UMR2000, CNRS, France
- The University of Hong Kong, China
- Sorbonne Université, France
- Institut Pasteur, France
Abstract
Evaluating the characteristics of emerging SARS-CoV-2 variants of concern is essential to inform pandemic risk assessment. A variant may grow faster if it produces a larger number of secondary infections ('R advantage') or if the timing of secondary infections (generation time) is better. So far, assessments have largely focused on deriving the R advantage assuming the generation time was unchanged. Yet, knowledge of both is needed to anticipate impact. Here we develop an analytical framework to investigate the contribution of both the R advantage and generation time to the growth advantage of a variant. It is known that selection on a variant with larger R increases with levels of transmission in the community. We additionally show that variants conferring earlier transmission are more strongly favoured when the historical strains have fast epidemic growth, while variants conferring later transmission are more strongly favoured when historical strains have slow or negative growth. We develop these conceptual insights into a new statistical framework to infer both the R advantage and generation time of a variant. On simulated data, our framework correctly estimates both parameters when it covers time periods characterized by different epidemiological contexts. Applied to data for the Alpha and Delta variants in England and in Europe, we find that Alpha confers a +54% [95% CI, 45-63%] R advantage compared to previous strains, and Delta +140% [98-182%] compared to Alpha, and mean generation times are similar to historical strains for both variants. This work helps interpret variant frequency dynamics and will strengthen risk assessment for future variants of concern.
Data availability
The codes used for the analyses are available at https://github.com/FrancoisBlanquart/selection_variantThe data used for the analysis is previously available data that is publicly available. A cleaned version of the data used for the analysis is also available herehttps://github.com/FrancoisBlanquart/selection_variant
Article and author information
Author details
François Blanquart
Benjamin John Cowling
Funding
Centre National de la Recherche Scientifique (Momentum to FB)
- François Blanquart
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Ben S Cooper, Mahidol University, Thailand
Version history
- Received: November 23, 2021
- Preprint posted: December 9, 2021 (view preprint)
- Accepted: May 8, 2022
- Accepted Manuscript published: May 19, 2022 (version 1)
- Version of Record published: June 17, 2022 (version 2)
- Version of Record updated: June 28, 2022 (version 3)
Copyright
© 2022, Blanquart et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Selection for infectivity profiles in slow and fast epidemics, and the rise of SARS-CoV-2 variants
eLife 11:e75791.
https://doi.org/10.7554/eLife.75791
Further reading
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- Epidemiology and Global Health
Background:
The Zanzibar archipelago of Tanzania has become a low-transmission area for Plasmodium falciparum. Despite being considered an area of pre-elimination for years, achieving elimination has been difficult, likely due to a combination of imported infections from mainland Tanzania and continued local transmission.
Methods:
To shed light on these sources of transmission, we applied highly multiplexed genotyping utilizing molecular inversion probes to characterize the genetic relatedness of 282 P. falciparum isolates collected across Zanzibar and in Bagamoyo district on the coastal mainland from 2016 to 2018.
Results:
Overall, parasite populations on the coastal mainland and Zanzibar archipelago remain highly related. However, parasite isolates from Zanzibar exhibit population microstructure due to the rapid decay of parasite relatedness over very short distances. This, along with highly related pairs within shehias, suggests ongoing low-level local transmission. We also identified highly related parasites across shehias that reflect human mobility on the main island of Unguja and identified a cluster of highly related parasites, suggestive of an outbreak, in the Micheweni district on Pemba island. Parasites in asymptomatic infections demonstrated higher complexity of infection than those in symptomatic infections, but have similar core genomes.
Conclusions:
Our data support importation as a main source of genetic diversity and contribution to the parasite population in Zanzibar, but they also show local outbreak clusters where targeted interventions are essential to block local transmission. These results highlight the need for preventive measures against imported malaria and enhanced control measures in areas that remain receptive to malaria reemergence due to susceptible hosts and competent vectors.
Funding:
This research was funded by the National Institutes of Health, grants R01AI121558, R01AI137395, R01AI155730, F30AI143172, and K24AI134990. Funding was also contributed from the Swedish Research Council, Erling-Persson Family Foundation, and the Yang Fund. RV acknowledges funding from the MRC Centre for Global Infectious Disease Analysis (reference MR/R015600/1), jointly funded by the UK Medical Research Council (MRC) and the UK Foreign, Commonwealth & Development Office (FCDO), under the MRC/FCDO Concordat agreement and is also part of the EDCTP2 program supported by the European Union. RV also acknowledges funding by Community Jameel.
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- Epidemiology and Global Health
- Microbiology and Infectious Disease
Background: Few national-level studies have evaluated the impact of 'hybrid' immunity (vaccination coupled with recovery from infection) from the Omicron variants of SARS-CoV-2.
Methods: From May 2020 to December 2022, we conducted serial assessments (each of ~4000-9000 adults) examining SARS-CoV-2 antibodies within a mostly representative Canadian cohort drawn from a national online polling platform. Adults, most of whom were vaccinated, reported viral test-confirmed infections and mailed self-collected dried blood spots to a central lab. Samples underwent highly sensitive and specific antibody assays to spike and nucleocapsid protein antigens, the latter triggered only by infection. We estimated cumulative SARS-CoV-2 incidence prior to the Omicron period and during the BA.1/1.1 and BA.2/5 waves. We assessed changes in antibody levels and in age-specific active immunity levels.
Results: Spike levels were higher in infected than in uninfected adults, regardless of vaccination doses. Among adults vaccinated at least thrice and infected more than six months earlier, spike levels fell notably and continuously for the nine months post-vaccination. By contrast, among adults infected within six months, spike levels declined gradually. Declines were similar by sex, age group, and ethnicity. Recent vaccination attenuated declines in spike levels from older infections. In a convenience sample, spike antibody and cellular responses were correlated. Near the end of 2022, about 35% of adults above age 60 had their last vaccine dose more than six months ago, and about 25% remained uninfected. The cumulative incidence of SARS-CoV-2 infection rose from 13% (95% CI 11-14%) before omicron to 78% (76-80%) by December 2022, equating to 25 million infected adults cumulatively. However, the COVID-19 weekly death rate during the BA.2/5 waves was less than half of that during the BA.1/1.1 wave, implying a protective role for hybrid immunity.
Conclusions: Strategies to maintain population-level hybrid immunity require up-to-date vaccination coverage, including among those recovering from infection. Population-based, self-collected dried blood spots are a practicable biological surveillance platform.
Funding: Funding was provided by the COVID-19 Immunity Task Force, Canadian Institutes of Health Research, Pfizer Global Medical Grants, and St. Michael's Hospital Foundation. PJ and ACG are funded by the Canada Research Chairs Program.
