Wastewater monitoring outperforms case numbers as a tool to track COVID-19 incidence dynamics when test positivity rates are high

Abstract

Wastewater-based epidemiology (WBE) has been shown to coincide with, or anticipate, confirmed COVID-19 case numbers. During periods with high test positivity rates, however, case numbers may be underreported, whereas wastewater does not suffer from this limitation. Here we investigated how the dynamics of new COVID-19 infections estimated based on wastewater monitoring or confirmed cases compare to true COVID-19 incidence dynamics. We focused on the first pandemic wave in Switzerland (February to April, 2020), when test positivity ranged up to 26%. SARS-CoV-2 RNA loads were determined 2-4 times per week in three Swiss wastewater treatment plants (Lugano, Lausanne and Zurich). Wastewater and case data were combined with a shedding load distribution and an infection-to-case confirmation delay distribution, respectively, to estimate incidence dynamics. Finally, the estimates were compared to reference incidence dynamics determined by a validated compartmental model. Incidence dynamics estimated based on wastewater data were found to better track the timing and shape of the reference infection peak compared to estimates based on confirmed cases. In contrast, case confirmations provided a better estimate of the subsequent decline in infections. Under a regime of high-test positivity rates, WBE thus provides critical information that is complementary to clinical data to monitor the pandemic trajectory.

Effect of storage conditions on SARS-CoV-2 RNA quantification in wastewater solids

“…Our results regarding wastewater solids stored at 4 °C are similar to those presented in these influent studies, except for Fernandez-Cassi et al (2021) ; overall we saw minimal reduction (less than an order of magnitude) even for samples stored over 100 days. However, the effect of freeze thaw on our measurements with solids is small compared to those reported by Markt et al (2021) and Fernandez-Cassi et al (2021) for infuent. We could identify only one published study on SARS-CoV-2 RNA decay in solids: Hokajärvi et al (2021) report minimal decay (between 0% and 20%) of SARS-CoV-2 RNA solids pelleted rom raw influent by centrifugation during storage at 4 °C, −20 °C, and −75 °C for 84 days, within the range of results reported herein.…”

“… Markt et al (2021) found minimal differences in SARS-CoV-2 RNA concentrations measured in influent stored for up to 7 days at 4 °C compared to concentrations measured with no storage, but found more than an order of magnitude decrease in SARS-CoV-2 RNA concentrations in samples that were stored frozen and subject to a freeze thaw. Fernandez-Cassi et al (2021) report extensive reduction in SARS-CoV-2 RNA concentrations measured in liquid wastewater stored at 4 °C and −20 °C (1–2 orders of magnitude). Our results regarding wastewater solids stored at 4 °C are similar to those presented in these influent studies, except for Fernandez-Cassi et al (2021) ; overall we saw minimal reduction (less than an order of magnitude) even for samples stored over 100 days.…”

“… Fernandez-Cassi et al (2021) report extensive reduction in SARS-CoV-2 RNA concentrations measured in liquid wastewater stored at 4 °C and −20 °C (1–2 orders of magnitude). Our results regarding wastewater solids stored at 4 °C are similar to those presented in these influent studies, except for Fernandez-Cassi et al (2021) ; overall we saw minimal reduction (less than an order of magnitude) even for samples stored over 100 days. However, the effect of freeze thaw on our measurements with solids is small compared to those reported by Markt et al (2021) and Fernandez-Cassi et al (2021) for infuent.…”

Wastewater Surveillance during Mass COVID-19 Vaccination on a College Campus

“… 12 − 44 More recently, SARS-CoV-2 RNA measurements in wastewater have been used to estimate the reproductive number during COVID-19 epidemics 14 with some finding wastewater outperforms clinical testing to estimate COVID-19 incidence during periods of “high [clinical] positivity” (>26%). 15 Importantly, the effectiveness of vaccines, including the BNT162b2 mRNA vaccine, against shedding of SARS-CoV-2 RNA remains uncertain, 16 , 17 as is the resulting effect on wastewater monitoring strategies and design.…”

The Rapid Assessment of Aggregated Wastewater Samples for Genomic Surveillance of SARS-CoV-2 on a City-Wide Scale

“…The clinical prevalence of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in the early stages of the pandemic led to the application of wastewater surveillance over a range of scales-from pooled sources covering large swaths of a community encompassing hundreds of thousands of individuals, to relatively isolated samples consisting of dozens to hundreds of individuals living in congregate settings [1][2][3][4][5][6]. These efforts were initially designed to monitor the trends of "true" incidence of SARS-CoV-2 infection within the targeted communities, as wastewater sampling represents a non-invasive means of quantitatively assessing the presence of SARS-CoV-2 nucleic acid derived from individuals participating and non-participating in clinical testing efforts [1,[7][8][9][10][11][12].…”