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      Correlation between SARS-CoV-2 RNA concentration in wastewater and COVID-19 cases in community: A systematic review and meta-analysis

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          Abstract

          Wastewater-based epidemiology (WBE) has been considered as a promising approach for population-wide surveillance of coronavirus disease 2019 (COVID-19). Many studies have successfully quantified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA concentration in wastewater ( C RNA). However, the correlation between the C RNA and the COVID-19 clinically confirmed cases in the corresponding wastewater catchments varies and the impacts of environmental and other factors remain unclear. A systematic review and meta-analysis were conducted to identify the correlation between C RNA and various types of clinically confirmed case numbers, including prevalence and incidence rates. The impacts of environmental factors, WBE sampling design, and epidemiological conditions on the correlation were assessed for the same datasets. The systematic review identified 133 correlation coefficients, ranging from -0.38 to 0.99. The correlation between C RNA and new cases (either daily new, weekly new, or future cases) was stronger than that of active cases and cumulative cases. These correlation coefficients were potentially affected by environmental and epidemiological conditions and WBE sampling design. Larger variations of air temperature and clinical testing coverage, and the increase of catchment size showed strong negative impacts on the correlation between C RNA and COVID-19 case numbers. Interestingly, the sampling technique had negligible impact although increasing the sampling frequency improved the correlation. These findings highlight the importance of viral shedding dynamics, in-sewer decay, WBE sampling design and clinical testing on the accurate back-estimation of COVID-19 case numbers through the WBE approach.

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          Viral load of SARS-CoV-2 in clinical samples

          Yang Pan, Daitao Zhang, Peng Yang … (2020)
          An outbreak caused by a novel human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in Wuhan in December 2019, 1 and has since spread within China and to other countries. Real-time RT-PCR assays are recommended for diagnosis of SARS-CoV-2 infection. 2 However, viral dynamics in infected patients are still yet to be fully determined. Here, we report our findings from different types of clinical specimens collected from 82 infected individuals. Serial samples (throat swabs, sputum, urine, and stool) from two patients in Beijing were collected daily after their hospitalisation (patient 1, days 3–12 post-onset; patient 2, days 4–15 post-onset). These samples were examined by an N-gene-specific quantitative RT-PCR assay, as described elsewhere. 3 The viral loads in throat swab and sputum samples peaked at around 5–6 days after symptom onset, ranging from around 104 to 107 copies per mL during this time (figure A, B ). This pattern of changes in viral load is distinct from the one observed in patients with SARS, which normally peaked at around 10 days after onset. 4 Sputum samples generally showed higher viral loads than throat swab samples. No viral RNA was detected in urine or stool samples from these two patients. Figure Viral dynamics of SARS-CoV-2 in infected patients Viral load (mean [SD]) from serial throat swab and sputum samples in patient 1 (A) and patient 2 (B). (C) Viral load (median [IQR]) in throat and sputum samples collected from 80 patients at different stages after disease onset. (D) Correlation between viral load in throat swab samples and viral load in sputum samples. We also studied respiratory samples (nasal [n=1] and throat swabs [n=67], and sputum [n=42]) collected from 80 individuals at different stages of infection. The viral loads ranged from 641 copies per mL to 1·34 × 1011 copies per mL, with a median of 7·99 × 104 in throat samples and 7·52 × 105 in sputum samples (figure C). The only nasal swab tested in this study (taken on day 3 post-onset) showed a viral load of 1·69 × 105 copies per mL. Overall, the viral load early after onset was high (>1 × 106 copies per mL). However, a sputum sample collected on day 8 post-onset from a patient who died had a very high viral load (1·34 × 1011 copies per mL). Notably, two individuals, who were under active surveillance because of a history of exposure to SARS-CoV-2-infected patients showed positive results on RT-PCR a day before onset, suggesting that infected individuals can be infectious before them become symptomatic. Among the 30 pairs of throat swab and sputum samples available, viral loads were significantly correlated between the two sample types for days 1–3 (R2=0·50, p=0·022), days 4–7 (R2=0·93, p<0·001), and days 7–14 (R2=0·95, p=0·028). From 17 confirmed cases of SARS-CoV-2 infection with available data (representing days 0–13 after onset), stool samples from nine (53%; days 0–11 after onset) were positive on RT-PCR analysis. Although the viral loads were less than those of respiratory samples (range 550 copies per mL to 1·21 × 105 copies per mL), precautionary measures should be considered when handling faecal samples.
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            First confirmed detection of SARS-CoV-2 in untreated wastewater in Australia: A proof of concept for the wastewater surveillance of COVID-19 in the community

            Warish Ahmed, Nicola Angel, Janette Edson … (2020)
            Infection with SARS-CoV-2, the etiologic agent of the ongoing COVID-19 pandemic, is accompanied by the shedding of the virus in stool. Therefore, the quantification of SARS-CoV-2 in wastewater affords the ability to monitor the prevalence of infections among the population via wastewater-based epidemiology (WBE). In the current work, SARS-CoV-2 RNA was concentrated from wastewater in a catchment in Australia and viral RNA copies were enumerated using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) resulting in two positive detections within a six day period from the same wastewater treatment plant (WWTP). The estimated RNA copy numbers observed in the wastewater were then used to estimate the number of infected individuals in the catchment via Monte Carlo simulation. Given the uncertainty and variation in the input parameters, the model estimated a median range of 171 to 1090 infected persons in the catchment, which is in reasonable agreement with clinical observations. This work highlights the viability of WBE for monitoring infectious diseases, such as COVID-19, in communities. The work also draws attention to the need for further methodological and molecular assay validation for enveloped viruses in wastewater.
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              Presence of SARS-Coronavirus-2 RNA in Sewage and Correlation with Reported COVID-19 Prevalence in the Early Stage of the Epidemic in The Netherlands

              Gertjan Medema, Leo Heijnen, Goffe S Elsinga … (2020)
              In the current COVID-19 pandemic, a significant proportion of cases shed SARS-Coronavirus-2 (SARS-CoV-2) with their faeces. To determine if SARS-CoV-2 RNA was present in sewage during the emergence of COVID-19 in The Netherlands, sewage samples of six cities and the airport were tested using four qRT-PCR assays, three targeting the nucleocapsid gene (N1–N3) and one the envelope gene (E). No SARS-CoV-2 RNA was detected on February 6, 3 weeks before the first Dutch case was reported. On March 4/5, one or more gene fragments were detected in sewage of three sites, in concentrations of 2.6–30 gene copies per mL. In Amersfoort, N3 was detected in sewage 6 days before the first cases were reported. As the prevalence of COVID-19 in these cities increased in March, the RNA signal detected by each qRT-PCR assay increased, for N1–N3 up to 790–2200 gene copies per mL. This increase correlated significantly with the increase in reported COVID-19 prevalence. The detection of the virus RNA in sewage, even when the COVID-19 prevalence is low, and the correlation between concentration in sewage and reported prevalence of COVID-19, indicate that sewage surveillance could be a sensitive tool to monitor the circulation of the virus in the population.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Hazard Mater
                Journal ID (iso-abbrev): J Hazard Mater
                Title: Journal of Hazardous Materials
                Publisher: Elsevier B.V.
                ISSN (Print): 0304-3894
                ISSN (Electronic): 1873-3336
                Publication date PMC-release: 27 August 2022
                Publication date (Electronic): 27 August 2022
                Electronic Location Identifier: 129848
                Affiliations
                [a ]School of Civil, Mining and Environmental Engineering, University of Wollongong, Wollongong, Australia
                [b ]Centre for Technology in Water and Wastewater, School of Civil and Environmental Engineering, University of Technology Sydney, Ultimo, NSW 2007, Australia
                [c ]Department of Environmental Health Sciences, Tulane University, New Orleans, LA, 70112
                [d ]NanoBioCel Group, Laboratory of Pharmaceutics, School of Pharmacy, University of the Basque Country UPV/EHU, Paseo de la Universidad 7, Vitoria-Gasteiz 01006, Spain
                [e ]Biomedical Research Networking Centre in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN). Vitoria-Gasteiz, Spain
                [f ]Bioaraba Health Research Institute; Osakidetza Basque Health Service, Araba Mental Health Network, Araba Psychiatric Hospital, Pharmacy Service, Vitoria-Gasteiz, Spain
                [g ]Interdisciplinary Center for River Basin Environment, University of Yamanashi, Kofu, Japan
                [h ]Faculty of Geosciences and Civil Engineering, Kanazawa University, Kanazawa, Japan
                [i ]Sustainability Cluster, School of Engineering, University of Petroleum and Energy Studies, Dehradun, Uttarakhand, India
                [j ]Dr. B. Lal Institute of Biotechnology, Jaipur, India
                [k ]Division of Environmental Engineering, Faculty of Engineering, Hokkaido University, Hokkaido, Japan
                [l ]Illawarra Health and Medical Research Institute (IHMRI), University of Wollongong, Wollongong, Australia
                Author notes
                [* ]Corresponding author at: School of Civil, Mining and Environmental Engineering, University of Wollongong, Wollongong, Australia
                Article
                Publisher Item ID: S0304-3894(22)01641-7 Publisher ID: 129848
                DOI: 10.1016/j.jhazmat.2022.129848
                PMC ID: 9420035
                PubMed ID: 36067562
                SO-VID: 6c2c99e3-c5d9-4182-9de5-8ee609d9f1a0
                Copyright © © 2022 Elsevier B.V. All rights reserved.
                License:

                Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

                History
                Date received : 26 April 2022
                Date revision received : 22 August 2022
                Date accepted : 23 August 2022
                Categories
                Subject: Review

                Keywords: covid-19,sars-cov-2,wastewater-based epidemiology,prevalence,incidence, clinical testing,viral shedding
                Data availability:
                Keywords: covid-19, sars-cov-2, wastewater-based epidemiology, prevalence, incidence, clinical testing, viral shedding

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