Low Testing Rates Limit the Ability of Genomic Surveillance Programs to Monitor SARS-CoV-2 Variants: A Mathematical Modelling Study

Han, Alvin X.; Toporowski, Amy; Sacks, Jilian A.; Perkins, Mark D.; Briand, Sylvie; Kerkhove, Maria D. Van; Hannay, Emma; Carmona, Sergio; Rodriguez, Bill; Parker, Edyth; Nichols, Brooke E; Russell, Colin A.

doi:10.2139/ssrn.4115475

Cited by 6 publications

(8 citation statements)

References 13 publications

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“…This can be used to inform the design of genomic surveillance programs for different pathogens by adapting the simulation parameters and scenarios. Our findings extend existing literature on estimating the rate of under-reporting during outbreaks and the effect on estimators of outbreak parameters (11,33,34), and guidelines for the design of genomic surveillance programs (1,5,16). An important strength of our method is that both clustering methods are based on arbitrary dissimilarity measures and as such can be extended to include other data types.…”

Section: Figuresupporting

confidence: 76%

“…The European Centre for Disease Prevention and Control (ECDC) published guidelines based on statistical considerations for the minimum number of sequences necessary to detect new variants or changes in the proportion of variants assuming representative sampling ( 5 ). Recent work has sought to improve the practical utility of these guidelines by simulating or modeling the steps in between infection with SARS-CoV-2 and genomic characterization ( 16 , 17 ). These approaches are important because they explicitly account for the effect of some sources of selection bias.…”

Section: Introductionmentioning

confidence: 99%

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Guiding the design of SARS-CoV-2 genomic surveillance by estimating the resolution of outbreak detection

Suster

Arnott²,

Blackwell³

et al. 2022

Front. Public Health

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Genomic surveillance of SARS-CoV-2 has been essential to inform public health response to outbreaks. The high incidence of infection has resulted in a smaller proportion of cases undergoing whole genome sequencing due to finite resources. We present a framework for estimating the impact of reduced depths of genomic surveillance on the resolution of outbreaks, based on a clustering approach using pairwise genetic and temporal distances. We apply the framework to simulated outbreak data to show that outbreaks are detected less frequently when fewer cases are subjected to whole genome sequencing. The impact of sequencing fewer cases depends on the size of the outbreaks, and on the genetic and temporal similarity of the index cases of the outbreaks. We also apply the framework to an outbreak of the SARS-CoV-2 Delta variant in New South Wales, Australia. We find that the detection of clusters in the outbreak would have been delayed if fewer cases had been sequenced. Existing recommendations for genomic surveillance estimate the minimum number of cases to sequence in order to detect and monitor new virus variants, assuming representative sampling of cases. Our method instead measures the resolution of clustering, which is important for genomic epidemiology, and accommodates sampling biases.

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Section: Figuresupporting

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Guiding the design of SARS-CoV-2 genomic surveillance by estimating the resolution of outbreak detection

Suster

Arnott²,

Blackwell³

et al. 2022

Front. Public Health

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show abstract

“…Although the percentage of reported cases sequenced in African countries (0.01 to 10%, mean = 1.27%) is not far from global figures (0.01 to 16%, mean = 1.31%), testing rates and infection-to-detection ratios in Africa were some of the lowest globally (38,62). Together with estimates of excess mortality being as much as 20-fold greater than the reported numbers in African countries (63), these are strong indications of undetected and underreported epidemic sizes in Africa, leading to undersampling of genomic data (62) and thus underestimates of viral exchange inferences in our study. Some countries with no publicly available SARS-CoV-2 sequences are, by definition, completely missing in our inference.…”

Section: Discussion Limitations and Conclusionmentioning

confidence: 97%

“…61 Marien Ngouabi, Brazzaville, Republic of the Congo. 62 Kwame Nkrumah University of Science and Technology, Department of Theoretical and Applied Biology, Kumasi, Ghana. 63 Kumasi Centre for Collaborative Research in Tropical Medicine, Kwame Nkrumah University of Science and Technology, Kumasi, Ghana.…”

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confidence: 99%

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

Tegally

San

Cotten

et al. 2022

Science

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Investment in SARS-CoV-2 sequencing in Africa over the past year has led to a major increase in the number of sequences generated, now exceeding 100,000 genomes, used to track the pandemic on the continent. Our results show an increase in the number of African countries able to sequence domestically, and highlight that local sequencing enables faster turnaround time and more regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and shed light on the distinct dispersal dynamics of Variants of Concern, particularly Alpha, Beta, Delta, and Omicron, on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve, while the continent faces many emerging and re-emerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century.

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“…As such, a robust level of surveillance efforts should still be maintained in these dominant source locations to provide timely actionable information on novel variant detection as well as infection control. These surveillance efforts should encompass a minimal level of clinical diagnostic testing capacity be maintained to ensure clinical genomic surveillance remains sensitive enough for early detection of novel variants ( Han et al, 2022 ). Wastewater surveillance could also be included to facilitate early variant detection and identify cryptic transmissions amid falling testing rates ( Karthikeyan et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Regional importation and asymmetric within-country spread of SARS-CoV-2 variants of concern in the Netherlands

Han

Kozanli

Koopsen

et al. 2022

eLife

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Background:Variants of concern (VOCs) of SARS-CoV-2 have caused resurging waves of infections worldwide. In the Netherlands, the Alpha, Beta, Gamma, and Delta VOCs circulated widely between September 2020 and August 2021. We sought to elucidate how various control measures, including targeted flight restrictions, had impacted the introduction and spread of these VOCs in the Netherlands.Methods:We performed phylogenetic analyses on 39,844 SARS-CoV-2 genomes collected under the Dutch national surveillance program.Results:We found that all four VOCs were introduced before targeted flight restrictions were imposed on countries where the VOCs first emerged. Importantly, foreign introductions, predominantly from other European countries, continued during these restrictions. After their respective introductions into the Netherlands, the Alpha and Delta VOCs largely circulated within more populous regions of the country with international connections before asymmetric bidirectional transmissions occurred with the rest of the country and the VOC became the dominant circulating lineage.Conclusions:Our findings show that flight restrictions had limited effectiveness in deterring VOC introductions due to the strength of regional land travel importation risks. As countries consider scaling down SARS-CoV-2 surveillance efforts in the post-crisis phase of the pandemic, our results highlight that robust surveillance in regions of early spread is important for providing timely information for variant detection and outbreak control.Funding:None.

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Low Testing Rates Limit the Ability of Genomic Surveillance Programs to Monitor SARS-CoV-2 Variants: A Mathematical Modelling Study

Cited by 6 publications

References 13 publications

Guiding the design of SARS-CoV-2 genomic surveillance by estimating the resolution of outbreak detection

Guiding the design of SARS-CoV-2 genomic surveillance by estimating the resolution of outbreak detection

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

Regional importation and asymmetric within-country spread of SARS-CoV-2 variants of concern in the Netherlands

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