Modeling infection from SARS-CoV-2 wastewater concentrations: promise, limitations, and future directions

Abstract

Estimating total infection levels, including unreported and asymptomatic infections, is important for understanding community disease transmission. Wastewater can provide a pooled community sample to estimate total infections that is independent of case reporting biases toward individuals with moderate to severe symptoms and by test-seeking behavior and access. We derive three mechanistic models for estimating community infection levels from wastewater measurements based on a description of the processes that generate SARS-CoV-2 RNA signals in wastewater and accounting for the fecal strength of wastewater through endogenous microbial markers, daily flow, and per-capita wastewater generation estimates. The models are illustrated through two case studies of wastewater data collected during 2020–2021 in Virginia Beach, VA, and Santa Clara County, CA. Median simulated infection levels generally were higher than reported cases, but at times, were lower, suggesting a discrepancy between the reported cases and wastewater data, or inaccurate modeling results. Daily simulated infection estimates showed large ranges, in part due to dependence on highly variable clinical viral fecal shedding data. Overall, the wastewater-based mechanistic models are useful for normalization of wastewater measurements and for understanding wastewater-based surveillance data for public health decision-making but are currently limited by lack of robust SARS-CoV-2 fecal shedding data.

Wastewater surveillance of human influenza, metapneumovirus, parainfluenza, respiratory syncytial virus (RSV), rhinovirus, and seasonal coronaviruses during the COVID-19 pandemic

“…Conversely, IBV and RSV A concentrations were lowest suggesting limited circulation of those viruses. Future work is needed to document time varying patterns of respiratory viral RNA inputs from infected individuals to the wastewater system to enable modeling of the number of infected individuals in a sewershed from wastewater viral RNA concentrations 27 and to enable modeling of epidemiological parameters like the reproductive number from wastewater data 28 .…”

Wastewater as a back door to serology?

“…Where that information is available, ELISA optical density or titer measurements may be extrapolated to a bulk copies per person measurement, in a way that is analogous to the handling of viral copy number data. 29 Because the protocol is able to detect antibodies in frozen archived wastewater samples, it becomes possible to analyze the SARS-CoV-2 pandemic retrospectively and to develop such models while simultaneously testing their predictive value against historic incidence levels. Leveraging existing samples collected throughout the COVID-19 pandemic to conduct historic longitudinal studies that simultaneously quantify concentrations of antibodies and integrate that information with viral load and case data for the corresponding sewershed population.…”

Significance of Wastewater Surveillance in Detecting the Prevalence of SARS-CoV-2 Variants and Other Respiratory Viruses in the Community – A Multi-Site Evaluation

“…15-17 It has also been shown that WBE of SARS-CoV-2 has a strong correlation with clinically diagnosed case numbers; 12 further, the WBE methodology is not dependent on external factors (e.g., testing and reporting rates, reporting lag, and reporting biases). 12,18,19…”

“…[15][16][17] It has also been shown that WBE of SARS-CoV-2 has a strong correlation with clinically diagnosed case numbers; 12 further, the WBE methodology is not dependent on external factors (e.g., testing and reporting rates, reporting lag, and reporting biases). 12,18,19 In this study, we captured and enriched SARS-CoV-2 in the wastewater, reported sitespecific sequencing and variant analysis, and described the implications of these data. Further, we performed a respiratory viral pathogens (RVP) panel analysis for other respiratory diseasecausing viruses in these samples.…”