A nationwide indicator to smooth and normalize heterogeneous SARS-CoV-2 RNA data in wastewater

[Display omitted] •A wastewater indicator has been designed and tested over the course of a large scale project.•It is based on a smoothing technique reducing measurement noise by 19%.•It takes into account the differences between laboratory quantification methods.•It also accounts for dilution effe...

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Published inEnvironment international Vol. 158; no. 106998; p. 106998
Main Authors Cluzel, Nicolas, Courbariaux, Marie, Wang, Siyun, Moulin, Laurent, Wurtzer, Sébastien, Bertrand, Isabelle, Laurent, Karine, Monfort, Patrick, Gantzer, Christophe, Guyader, Soizick Le, Boni, Mickaël, Mouchel, Jean-Marie, Maréchal, Vincent, Nuel, Grégory, Maday, Yvon
Format Journal Article
LanguageEnglish
Published Netherlands Elsevier Ltd 01.01.2022
Elsevier
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Abstract [Display omitted] •A wastewater indicator has been designed and tested over the course of a large scale project.•It is based on a smoothing technique reducing measurement noise by 19%.•It takes into account the differences between laboratory quantification methods.•It also accounts for dilution effects such as precipitation.•Its good correlation with the incidence rate could make it a credible alternative to mass testing. Since many infected people experience no or few symptoms, the SARS-CoV-2 epidemic is frequently monitored through massive virus testing of the population, an approach that may be biased and may be difficult to sustain in low-income countries. Since SARS-CoV-2 RNA can be detected in stool samples, quantifying SARS-CoV-2 genome by RT-qPCR in wastewater treatment plants (WWTPs) has been carried out as a complementary tool to monitor virus circulation among human populations. However, measuring SARS-CoV-2 viral load in WWTPs can be affected by many experimental and environmental factors. To circumvent these limits, we propose here a novel indicator, the wastewater indicator (WWI), that partly reduces and corrects the noise associated with the SARS-CoV-2 genome quantification in wastewater (average noise reduction of 19%). All data processing results in an average correlation gain of 18% with the incidence rate. The WWI can take into account the censorship linked to the limit of quantification (LOQ), allows the automatic detection of outliers to be integrated into the smoothing algorithm, estimates the average measurement error committed on the samples and proposes a solution for inter-laboratory normalization in the absence of inter-laboratory assays (ILA). This method has been successfully applied in the context of Obépine, a French national network that has been quantifying SARS-CoV-2 genome in a representative sample of French WWTPs since March 5th 2020. By August 26th, 2021, 168 WWTPs were monitored in the French metropolitan and overseas territories of France. We detail the process of elaboration of this indicator, show that it is strongly correlated to the incidence rate and that the optimal time lag between these two signals is only a few days, making our indicator an efficient complement to the incidence rate. This alternative approach may be especially important to evaluate SARS-CoV-2 dynamics in human populations when the testing rate is low.
AbstractList Since many infected people experience no or few symptoms, the SARS-CoV-2 epidemic is frequently monitored through massive virus testing of the population, an approach that may be biased and may be difficult to sustain in low-income countries. Since SARS-CoV-2 RNA can be detected in stool samples, quantifying SARS-CoV-2 genome by RT-qPCR in wastewater treatment plants (WWTPs) has been carried out as a complementary tool to monitor virus circulation among human populations. However, measuring SARS-CoV-2 viral load in WWTPs can be affected by many experimental and environmental factors. To circumvent these limits, we propose here a novel indicator, the wastewater indicator (WWI), that partly reduces and corrects the noise associated with the SARS-CoV-2 genome quantification in wastewater (average noise reduction of 19%). All data processing results in an average correlation gain of 18% with the incidence rate. The WWI can take into account the censorship linked to the limit of quantification (LOQ), allows the automatic detection of outliers to be integrated into the smoothing algorithm, estimates the average measurement error committed on the samples and proposes a solution for inter-laboratory normalization in the absence of inter-laboratory assays (ILA). This method has been successfully applied in the context of Obépine, a French national network that has been quantifying SARS-CoV-2 genome in a representative sample of French WWTPs since March 5th 2020. By August 26th, 2021, 168 WWTPs were monitored in the French metropolitan and overseas territories of France. We detail the process of elaboration of this indicator, show that it is strongly correlated to the incidence rate and that the optimal time lag between these two signals is only a few days, making our indicator an efficient complement to the incidence rate. This alternative approach may be especially important to evaluate SARS-CoV-2 dynamics in human populations when the testing rate is low.
[Display omitted] •A wastewater indicator has been designed and tested over the course of a large scale project.•It is based on a smoothing technique reducing measurement noise by 19%.•It takes into account the differences between laboratory quantification methods.•It also accounts for dilution effects such as precipitation.•Its good correlation with the incidence rate could make it a credible alternative to mass testing. Since many infected people experience no or few symptoms, the SARS-CoV-2 epidemic is frequently monitored through massive virus testing of the population, an approach that may be biased and may be difficult to sustain in low-income countries. Since SARS-CoV-2 RNA can be detected in stool samples, quantifying SARS-CoV-2 genome by RT-qPCR in wastewater treatment plants (WWTPs) has been carried out as a complementary tool to monitor virus circulation among human populations. However, measuring SARS-CoV-2 viral load in WWTPs can be affected by many experimental and environmental factors. To circumvent these limits, we propose here a novel indicator, the wastewater indicator (WWI), that partly reduces and corrects the noise associated with the SARS-CoV-2 genome quantification in wastewater (average noise reduction of 19%). All data processing results in an average correlation gain of 18% with the incidence rate. The WWI can take into account the censorship linked to the limit of quantification (LOQ), allows the automatic detection of outliers to be integrated into the smoothing algorithm, estimates the average measurement error committed on the samples and proposes a solution for inter-laboratory normalization in the absence of inter-laboratory assays (ILA). This method has been successfully applied in the context of Obépine, a French national network that has been quantifying SARS-CoV-2 genome in a representative sample of French WWTPs since March 5th 2020. By August 26th, 2021, 168 WWTPs were monitored in the French metropolitan and overseas territories of France. We detail the process of elaboration of this indicator, show that it is strongly correlated to the incidence rate and that the optimal time lag between these two signals is only a few days, making our indicator an efficient complement to the incidence rate. This alternative approach may be especially important to evaluate SARS-CoV-2 dynamics in human populations when the testing rate is low.
Since many infected people experience no or few symptoms, the SARS-CoV-2 epidemic is frequently monitored through massive virus testing of the population, an approach that may be biased and may be difficult to sustain in low-income countries. Since SARS-CoV-2 RNA can be detected in stool samples, quantifying SARS-CoV-2 genome by RT-qPCR in wastewater treatment plants (WWTPs) has been carried out as a complementary tool to monitor virus circulation among human populations. However, measuring SARS-CoV-2 viral load in WWTPs can be affected by many experimental and environmental factors. To circumvent these limits, we propose here a novel indicator, the wastewater indicator (WWI), that partly reduces and corrects the noise associated with the SARS-CoV-2 genome quantification in wastewater (average noise reduction of 19%). All data processing results in an average correlation gain of 18% with the incidence rate. The WWI can take into account the censorship linked to the limit of quantification (LOQ), allows the automatic detection of outliers to be integrated into the smoothing algorithm, estimates the average measurement error committed on the samples and proposes a solution for inter-laboratory normalization in the absence of inter-laboratory assays (ILA). This method has been successfully applied in the context of Obépine, a French national network that has been quantifying SARS-CoV-2 genome in a representative sample of French WWTPs since March 5th 2020. By August 26th, 2021, 168 WWTPs were monitored in the French metropolitan and overseas territories of France. We detail the process of elaboration of this indicator, show that it is strongly correlated to the incidence rate and that the optimal time lag between these two signals is only a few days, making our indicator an efficient complement to the incidence rate. This alternative approach may be especially important to evaluate SARS-CoV-2 dynamics in human populations when the testing rate is low.Since many infected people experience no or few symptoms, the SARS-CoV-2 epidemic is frequently monitored through massive virus testing of the population, an approach that may be biased and may be difficult to sustain in low-income countries. Since SARS-CoV-2 RNA can be detected in stool samples, quantifying SARS-CoV-2 genome by RT-qPCR in wastewater treatment plants (WWTPs) has been carried out as a complementary tool to monitor virus circulation among human populations. However, measuring SARS-CoV-2 viral load in WWTPs can be affected by many experimental and environmental factors. To circumvent these limits, we propose here a novel indicator, the wastewater indicator (WWI), that partly reduces and corrects the noise associated with the SARS-CoV-2 genome quantification in wastewater (average noise reduction of 19%). All data processing results in an average correlation gain of 18% with the incidence rate. The WWI can take into account the censorship linked to the limit of quantification (LOQ), allows the automatic detection of outliers to be integrated into the smoothing algorithm, estimates the average measurement error committed on the samples and proposes a solution for inter-laboratory normalization in the absence of inter-laboratory assays (ILA). This method has been successfully applied in the context of Obépine, a French national network that has been quantifying SARS-CoV-2 genome in a representative sample of French WWTPs since March 5th 2020. By August 26th, 2021, 168 WWTPs were monitored in the French metropolitan and overseas territories of France. We detail the process of elaboration of this indicator, show that it is strongly correlated to the incidence rate and that the optimal time lag between these two signals is only a few days, making our indicator an efficient complement to the incidence rate. This alternative approach may be especially important to evaluate SARS-CoV-2 dynamics in human populations when the testing rate is low.
ArticleNumber 106998
Author Moulin, Laurent
Gantzer, Christophe
Maréchal, Vincent
Maday, Yvon
Wurtzer, Sébastien
Bertrand, Isabelle
Laurent, Karine
Nuel, Grégory
Courbariaux, Marie
Mouchel, Jean-Marie
Guyader, Soizick Le
Cluzel, Nicolas
Boni, Mickaël
Monfort, Patrick
Wang, Siyun
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  organization: Sorbonne Université, Maison des Modélisations Ingénieries et Technologies (SUMMIT), 75005 Paris, France
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  organization: Ifremer, laboratoire de Microbiologie, SG2M/LSEM, BP 21105, 44311 Nantes, France
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  organization: Institut de Recherche Biomédicale des Armées, 1 place Valérie André, F-91220 Brétigny-sur-Orge, France
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  organization: Sorbonne Université, CNRS, EPHE, UMR 7619 Metis, e-LTER Zone Atelier Seine, F-75005 Paris, France
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  givenname: Vincent
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  organization: Sorbonne Université, INSERM, Centre de Recherche Saint-Antoine, F-75012 Paris, France
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  surname: Nuel
  fullname: Nuel, Grégory
  organization: Stochastics and Biology Group, Probability and Statistics (LPSM, CNRS 8001), Sorbonne University, Campus Pierre et Marie Curie, 4 Place Jussieu, 75005 Paris, France
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  email: yvon.maday@sorbonne-universite.fr
  organization: Sorbonne Université, CNRS, Université de Paris, Laboratoire Jacques-Louis Lions (LJLL), F-75005 Paris, France
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Issue 106998
Keywords CMILA
Correlation
EDQPI
LSM
WWI
Coronavirus infectious disease 19 (COVID-19)
CM
RMSE
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Sampling frequency
LOQ
EPCI
WWTP
COD
RMS
Wastewater-based epidemiology (WBE)
Mathematical modeling
BIC
ILA
Language English
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content type line 23
These authors contributed equally.
Obépine consortium includes Isabelle Bertrand, Soizick Le Guyader, Christophe Gantzer, Mickael Boni, Vincent Maréchal, Yvon Maday, Jean-Marie Mouchel, Laurent Moulin, Sébastien Wurtzer and Rémy Teyssou.
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Snippet [Display omitted] •A wastewater indicator has been designed and tested over the course of a large scale project.•It is based on a smoothing technique reducing...
Since many infected people experience no or few symptoms, the SARS-CoV-2 epidemic is frequently monitored through massive virus testing of the population, an...
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StartPage 106998
SubjectTerms algorithms
automatic detection
complement
Coronavirus infectious disease 19 (COVID-19)
Correlation
COVID-19
Ecology, environment
Emerging diseases
Environmental Engineering
Environmental Sciences
Epidemics
France
genome
Health
Human health and pathology
Humans
Infectious diseases
Life Sciences
Mathematical modeling
RNA
RNA, Viral
Sampling frequency
Santé publique et épidémiologie
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
viral load
viruses
Waste Water
wastewater
wastewater treatment
Wastewater-based epidemiology (WBE)
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Title A nationwide indicator to smooth and normalize heterogeneous SARS-CoV-2 RNA data in wastewater
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