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      Size and duration of COVID-19 clusters go along with a high SARS-CoV-2 viral load: A spatio-temporal investigation in Vaud state, Switzerland

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          Abstract

          To understand the geographical and temporal spread of SARS-CoV-2 during the first documented wave of infection in the state of Vaud, Switzerland, we analyzed clusters of positive cases using the precise residential location of 33,651 individuals tested (RT-PCR) between January 10 and June 30, 2020. We used a prospective Poisson space-time scan statistic (SaTScan) and a Modified Space–Time Density-Based Spatial Clustering of Application with Noise (MST-DBSCAN) to identify both space-time and transmission clusters, and estimated cluster duration, transmission behavior (emergence, growth, reduction, etc.) and relative risk. For each cluster, we computed the number of individuals, the median age of individuals and their viral load.

          Among the 1684 space-time clusters identified, 457 (27.1%) were significant ( p ≤ 0.05), such that they harbored a higher relative risk of infection within the cluster than compared to regions outside the cluster. Clusters lasted a median of 11 days (IQR 7–13) and included a median of 12 individuals per cluster (IQR 5–20). The majority of significant clusters ( n = 260; 56.9%) had at least one person with an extremely high viral load (>1 billion copies/ml). Those clusters were considerably larger (median of 17 infected individuals, p < 0.001) than clusters with individuals showing a viral load below 1 million copies/ml (median of three infected individuals). The highest viral loads were found in clusters with the lowest average age group considered in the investigation, while clusters with the highest average age had low to middle viral load. In 20 significant clusters, the viral load of the three first cases was below 100,000 copies/ml, suggesting that subjects with fewer than 100,000 copies/ml may still be contagious. Notably, the dynamics of transmission clusters made it possible to identify three diffusion zones, which predominantly differentiated between rural and urban areas, the latter being more prone to persistence and expansion, which may result in the emergence of new clusters nearby.

          The use of geographic information is key for public health decision makers in mitigating the spread of the SARS-CoV-2 virus. This study suggests that early localization of clusters may help implement targeted protective measures limiting the spread of the virus.

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          Most cited references53

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          Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR

          Background The ongoing outbreak of the recently emerged novel coronavirus (2019-nCoV) poses a challenge for public health laboratories as virus isolates are unavailable while there is growing evidence that the outbreak is more widespread than initially thought, and international spread through travellers does already occur. Aim We aimed to develop and deploy robust diagnostic methodology for use in public health laboratory settings without having virus material available. Methods Here we present a validated diagnostic workflow for 2019-nCoV, its design relying on close genetic relatedness of 2019-nCoV with SARS coronavirus, making use of synthetic nucleic acid technology. Results The workflow reliably detects 2019-nCoV, and further discriminates 2019-nCoV from SARS-CoV. Through coordination between academic and public laboratories, we confirmed assay exclusivity based on 297 original clinical specimens containing a full spectrum of human respiratory viruses. Control material is made available through European Virus Archive – Global (EVAg), a European Union infrastructure project. Conclusion The present study demonstrates the enormous response capacity achieved through coordination of academic and public laboratories in national and European research networks.
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            Fast unfolding of communities in large networks

            Journal of Statistical Mechanics: Theory and Experiment, 2008(10), P10008
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              Temporal profiles of viral load in posterior oropharyngeal saliva samples and serum antibody responses during infection by SARS-CoV-2: an observational cohort study

              Summary Background Coronavirus disease 2019 (COVID-19) causes severe community and nosocomial outbreaks. Comprehensive data for serial respiratory viral load and serum antibody responses from patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are not yet available. Nasopharyngeal and throat swabs are usually obtained for serial viral load monitoring of respiratory infections but gathering these specimens can cause discomfort for patients and put health-care workers at risk. We aimed to ascertain the serial respiratory viral load of SARS-CoV-2 in posterior oropharyngeal (deep throat) saliva samples from patients with COVID-19, and serum antibody responses. Methods We did a cohort study at two hospitals in Hong Kong. We included patients with laboratory-confirmed COVID-19. We obtained samples of blood, urine, posterior oropharyngeal saliva, and rectal swabs. Serial viral load was ascertained by reverse transcriptase quantitative PCR (RT-qPCR). Antibody levels against the SARS-CoV-2 internal nucleoprotein (NP) and surface spike protein receptor binding domain (RBD) were measured using EIA. Whole-genome sequencing was done to identify possible mutations arising during infection. Findings Between Jan 22, 2020, and Feb 12, 2020, 30 patients were screened for inclusion, of whom 23 were included (median age 62 years [range 37–75]). The median viral load in posterior oropharyngeal saliva or other respiratory specimens at presentation was 5·2 log10 copies per mL (IQR 4·1–7·0). Salivary viral load was highest during the first week after symptom onset and subsequently declined with time (slope −0·15, 95% CI −0·19 to −0·11; R 2=0·71). In one patient, viral RNA was detected 25 days after symptom onset. Older age was correlated with higher viral load (Spearman's ρ=0·48, 95% CI 0·074–0·75; p=0·020). For 16 patients with serum samples available 14 days or longer after symptom onset, rates of seropositivity were 94% for anti-NP IgG (n=15), 88% for anti-NP IgM (n=14), 100% for anti-RBD IgG (n=16), and 94% for anti-RBD IgM (n=15). Anti-SARS-CoV-2-NP or anti-SARS-CoV-2-RBD IgG levels correlated with virus neutralisation titre (R 2>0·9). No genome mutations were detected on serial samples. Interpretation Posterior oropharyngeal saliva samples are a non-invasive specimen more acceptable to patients and health-care workers. Unlike severe acute respiratory syndrome, patients with COVID-19 had the highest viral load near presentation, which could account for the fast-spreading nature of this epidemic. This finding emphasises the importance of stringent infection control and early use of potent antiviral agents, alone or in combination, for high-risk individuals. Serological assay can complement RT-qPCR for diagnosis. Funding Richard and Carol Yu, May Tam Mak Mei Yin, The Shaw Foundation Hong Kong, Michael Tong, Marina Lee, Government Consultancy Service, and Sanming Project of Medicine.
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                Author and article information

                Journal
                Sci Total Environ
                Sci Total Environ
                The Science of the Total Environment
                The Author(s). Published by Elsevier B.V.
                0048-9697
                1879-1026
                15 May 2021
                15 September 2021
                15 May 2021
                : 787
                : 147483
                Affiliations
                [a ]Laboratory of Geographic Information Systems (LASIG), School of Architecture, Civil and Environmental Engineering (ENAC), Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland
                [b ]Institute of Microbiology, University Hospital Centre and University of Lausanne, Switzerland
                [c ]Department of Emergency Medicine, Lausanne University Hospital, Rue du Bugnon 46, CH-1011 Lausanne, Switzerland
                [d ]Division and Department of Primary Care Medicine, Geneva University Hospitals, Geneva, Switzerland
                [e ]La Source School of Nursing, University of Applied Sciences and Arts Western Switzerland (HES-SO), Lausanne, Switzerland
                [f ]Unit of Population Epidemiology, Division of Primary Care, Geneva University Hospitals, Switzerland
                [g ]Group of Geographic Information Research and Analysis in Population Health (GIRAPH), Switzerland
                [h ]Infectious Diseases Service, University Hospital Centre, Lausanne, Switzerland
                Author notes
                [* ]Corresponding author at: Laboratory of geographic Information Systems (LASIG), Institute of Environmental Engineering (IIE), Ecole Polytechnique Fédérale de Lausanne (EPFL), GC Building - Station 18, 1015 Lausanne, Switzerland.
                [1]

                Equally contributed.

                Article
                S0048-9697(21)02554-7 147483
                10.1016/j.scitotenv.2021.147483
                8123367
                34000545
                cb19ed8e-9c5a-48c9-9853-445f8a7eb12c
                © 2021 The Author(s)

                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
                : 21 February 2021
                : 26 April 2021
                : 28 April 2021
                Categories
                Article

                General environmental science
                health geography,infectious disease,gis,coronavirus,contagiousness,spacetime scan statistic

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