Wastewater as a back door to serology?

Abstract

Wastewater surveillance is a powerful tool for monitoring the prevalence of infectious disease in urban populations, with predictive value for upcoming increases in cases and hospitalizations. The approach primarily used in disease surveillance has been to measure the number of viral copies detected in wastewater for a study area of known population, and systems for wastewater monitoring have been put in place worldwide during the SARS-CoV-2 pandemic. However, the potential to measure other biomarkers such as proteins and metabolites in wastewater has not been fully explored. Here we develop an approach to determine antibody optical density and titer measurements from wastewater. We measured abundance of anti-SARS-CoV-2 spike IgG and IgA from typical fresh samples of community wastewater, and from a collection of frozen samples dating from 2020-22. The assay described can be performed with readily available commercial reagents, at a moderate per-sample cost, facilitating non-invasive population level immune surveillance. Our findings demonstrate the feasibility of indirect serological surveillance through wastewater for population level monitoring, and the protocol described will enable the collection of larger data sets and development of models that can be leveraged to anticipate public health needs.

Sewage Protein Information Mining: Discovery of Large Biomolecules as Biomarkers of Population and Industrial Activities

“…15 More recently, measurement of specific Igs in wastewater was proposed as a window for community serology and an ELISA method was developed in the context of COVID surveillance. 18 Igs are large heterodimeric glycoproteins composed of two heavy and two light chains, each of which is a combination of different variable and constant domains encoded by 176 genes. There are five Ig isotypes named based on their α, Δ, ϵ, γ, and μ heavy chains (IgA, IgD, IgE, IgG, and IgM, respectively), each containing one of the two classes of light chains (κ and λ).…”

“…16 More recently, using ELISA analyses, quantitation of human immunoglobulins A and G in wastewater was reported and proposed as a tool for community serology. 18 Besides these works, most sewage proteomic studies have focused on the characterization of the microbiome in either sludge 19 or wastewater, 16,20 and the information on other human, animal, or vegetal proteins remains scarce at best.…”

<strong>The Lavatory Lens: Tracking the Global Movement of Pathogens via Aircraft Wastewater</strong>

“…80,81 Other analytical techniques that warrant further investigation include loop-mediated isothermal amplification (LAMP) and helicase-dependent amplification (HDA) which can return results in shorter time frames and have been implemented on lateral flow test strips in clinical and environmental settings. [82][83][84] More novel techniques that could become relevant include mass spectrometry for the detection of proteins relevant to specific pathogens 85 , enzyme-linked immunosorbent assays (ELISA) to detect specific antibodies 86 , or clustered regularly interspaced short palindromic repeats (CRISPR)-based diagnostic assays. 87,88 In contrast to targeted diagnostic techniques (e.g., PCR, LAMP, CRISPR), next generation sequencing (NGS) can offer semi-targeted or even untargeted analytical capabilities.…”

Urban wastewater contains a functional human antibody repertoire of mucosal origin

“…The demonstration of antibodies in wastewater is a potential first step towards tracking community immunity levels, opening the possibility of defining immune protection thresholds for a given pathogen and monitoring the efficacy of a mucosal vaccine campaign. Protein mass spectrometry has identified significant amounts of human Ig chain peptides in wastewater (18) and a preprint by Agan et al (19) found that wastewater collected at both building- and WRRF-scales contained SARS-CoV-2 specific IgG and IgA antibodies by enzyme-linked immunosorbent assay (ELISA). However, the extent of intact and functional human antibody pools in urban wastewaters remains unclear.…”