Predictive Potential of SARS-CoV-2 RNA Concentration in Wastewater to Assess the Dynamics of COVID-19 Clinical Outcomes and Infections

Coronavirus disease 2019 - caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) -, has triggered a worldwide pandemic resulting in 665 million infections and over 6.5 million deaths as of December 15, 2022. The development of different epidemiological tools have helped predict new outbreaks and assess the behavior of clinical variables in different health contexts. In this study, we aimed to monitor concentrations of SARS-CoV-2 in wastewater as a tool to predict the progression of clinical variables during Waves 3, 5, and 6 of the pandemic in the Spanish city of Xátiva from September 2020 to March 2022. We estimated SARS-CoV-2 RNA concentrations in 195 wastewater samples using the RT-PCR Diagnostic Panel validated by the Center for Disease Control and Prevention. We also compared the trends of several clinical variables (14-day cumulative incidence, positive cases, hospital cases and stays, critical cases and stays, primary care visits, and deaths) for each study wave against wastewater SARS-CoV-2 RNA concentrations using Pearson's product-moment correlations, a two-sided Mann-Whitney U test, and a cross-correlation analysis. We found strong correlations between SARS-CoV-2 concentrations with 14-day cumulative incidence and positive cases over time. Wastewater RNA concentrations showed strong correlations with these variables one and two weeks in advance. There were significant correlations with hospitalizations and critical care during Wave 3 and Wave 6; cross-correlations were stronger for hospitalization stays one week before during Wave 6. No association between vaccination percentages and wastewater viral concentrations was observed. Our findings support wastewater SARS-CoV-2 concentrations as a potential surveillance tool to anticipate infection and epidemiological data such as 14-day cumulative incidence, hospitalizations, and critical care stays. Public health authorities could use this epidemiological tool on a similar population as an aid for health care decision-making during an epidemic outbreak.