COVID-19 pandemic is ongoing for more than a year and has changed priorities and boosted some WBE studies. The aim of this work is to contributed to our knowledge sharing the methodology developed for SARS-CoV-2 detection in wastewater of Madrid region of over six million and a half inhabitants, where the sewer system is a combined system. At first, a pilot test in a small metropolitan area was carried out in order to define the criteria for the selection of the sampling points to be applied to the entire region. Methodologys for laboratory analysis and statistical analysis and interpretation of data are also presented. This work relies highly on fieldwork, so sewer network safe accessibility is paramount. A total of 289 sampling points were weekly characterised. Each sampling point represents a sewershed, some of them in a cascade distribution. Samples are tested for SARS-CoV-2 concentration (gc/L, genome copies per litre) and physicochemical parameters are also analysed to validate or discard what at first could be an unusual virus presence. Field results are correlated with health indicators such as incidence rates and hospitalisation data. This information is daily shared with regional health authorities, disaggregated by municipalities, or aggregated for the entire Madrid region. Results have proved to anticipate health indicators. The tool is used as an early warning indicator for COVID-19 pandemic. Further work is planned to apply the current scheme for a permanent epidemiological surveillance system of 87 sampling points to pinpoint infection hotspots and activate the linked sewersheds in the event of an outbreak.