Modelling patterns of SARS-CoV-2 circulation in the Netherlands, August 2020-February 2022, revealed by a nationwide sewage surveillance program

Background Surveillance of SARS-CoV-2 in wastewater offers an unbiased and near real-time tool to track circulation of SARS-CoV-2 at a local scale, next to other epidemic indicators such as hospital admissions and test data. However, individual measurements of SARS-CoV-2 in sewage are noisy, inherently variable, and can be left-censored. Aim We aimed to infer latent virus loads in a comprehensive sewage surveillance program that includes all sewage treatment plants (STPs) in the Netherlands and covers 99.6% of the Dutch population. Methods A multilevel Bayesian penalized spline model was developed and applied to estimate time- and STP-specific virus loads based on water flow adjusted SARS-CoV-2 qRT-PCR data from 1-4 sewage samples per week for each of the >300 STPs. Results The model provided an adequate fit to the data and captured the epidemic upsurges and downturns in the Netherlands, despite substantial day-to-day measurement variation. Estimated STP virus loads varied by more than two orders of magnitude, from approximately 1012 (virus particles per 100,000 persons per day) in the epidemic trough in August 2020 to almost 1015 in many STPs in January 2022. Epidemics at the local levels were slightly shifted between STPs and municipalities, which resulted in less pronounced peaks and troughs at the national level. Conclusion Although substantial day-to-day variation is observed in virus load measurements, wastewater-based surveillance of SARS-CoV-2 can track long-term epidemic progression at a local scale in near real-time, especially at high sampling frequency. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This research was financed by the Dutch Ministry of Health, Welfare and Sport, and by the Japan Society for the Promotion of Science (FM, JSPS KAKENHI Grant number 20J00793). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Data and code are publicly available at (data) and (code). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Data and code are publicly available at (data) and (code).