Caroline M Williams1, Daniel Pan2, Jonathan Decker3, Anika Wisniewska3, Eve Fletcher3, Shirley Sze4, Sara Assadi5, Richard Haigh3, Mohamad Abdulwhhab3, Paul Bird6, Christopher W Holmes6, Alaa Al-Taie7, Baber Saleem8, Jingzhe Pan8, Natalie J Garton3, Manish Pareek9, Michael R Barer10. 1. Department of Respiratory Sciences, University of Leicester, United Kingdom; Department of Clinical Microbiology, University Hospitals of Leicester NHS Trust, United Kingdom; Department of Infectious Diseases and HIV Medicine, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom. Electronic address: cw329@le.ac.uk. 2. Department of Respiratory Sciences, University of Leicester, United Kingdom; Department of Infectious Diseases and HIV Medicine, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom. 3. Department of Respiratory Sciences, University of Leicester, United Kingdom. 4. Department of Cardiovascular Sciences, University of Leicester, United Kingdom. 5. Department of Infectious Diseases and HIV Medicine, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom. 6. Department of Respiratory Sciences, University of Leicester, United Kingdom; Department of Clinical Microbiology, University Hospitals of Leicester NHS Trust, United Kingdom. 7. Department of Biomedical Engineering, Al-Nahrain University, Baghdad, Iraq. 8. Department of Engineering, University of Leicester, United Kingdom. 9. Department of Respiratory Sciences, University of Leicester, United Kingdom; Department of Infectious Diseases and HIV Medicine, University Hospitals of Leicester NHS Trust, Leicester, United Kingdom. Electronic address: mp4246@le.ac.uk. 10. Department of Respiratory Sciences, University of Leicester, United Kingdom; Department of Clinical Microbiology, University Hospitals of Leicester NHS Trust, United Kingdom. Electronic address: mrb19@le.ac.uk.
Abstract
BACKGROUND: Human to human transmission of SARS-CoV-2 is driven by the respiratory route but little is known about the pattern and quantity of virus output from exhaled breath. We have previously shown that face-mask sampling (FMS) can detect exhaled tubercle bacilli and have adapted its use to quantify exhaled SARS-CoV-2 RNA in patients admitted to hospital with Coronavirus Disease-2019 (COVID-19). METHODS: Between May and December 2020, we took two concomitant FMS and nasopharyngeal samples (NPS) over two days, starting within 24 h of a routine virus positive NPS in patients hospitalised with COVID-19, at University Hospitals of Leicester NHS Trust, UK. Participants were asked to wear a modified duckbilled facemask for 30 min, followed by a nasopharyngeal swab. Demographic, clinical, and radiological data, as well as International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) mortality and deterioration scores were obtained. Exposed masks were processed by removal, dissolution and analysis of sampling matrix strips fixed within the mask by RT-qPCR. Viral genome copy numbers were determined and results classified as Negative; Low: ≤999 copies; Medium: 1000-99,999 copies and High ≥ 100,000 copies per strip for FMS or per 100 µl for NPS. RESULTS: 102 FMS and NPS were collected from 66 routinely positive patients; median age: 61 (IQR 49 - 77), of which FMS was positive in 38% of individuals and concomitant NPS was positive in 50%. Positive FMS viral loads varied over five orders of magnitude (<10-3.3 x 106 genome copies/strip); 21 (32%) patients were asymptomatic at the time of sampling. High FMS viral load was associated with respiratory symptoms at time of sampling and shorter interval between sampling and symptom onset (FMS High: median (IQR) 2 days (2-3) vs FMS Negative: 7 days (7-10), p = 0.002). On multivariable linear regression analysis, higher FMS viral loads were associated with higher ISARIC mortality (Medium FMS vs Negative FMS gave an adjusted coefficient of 15.7, 95% CI 3.7-27.7, p = 0.01) and deterioration scores (High FMS vs Negative FMS gave an adjusted coefficient of 37.6, 95% CI 14.0 to 61.3, p = 0.002), while NPS viral loads showed no significant association. CONCLUSION: We demonstrate a simple and effective method for detecting and quantifying exhaled SARS-CoV-2 in hospitalised patients with COVID-19. Higher FMS viral loads were more likely to be associated with developing severe disease compared to NPS viral loads. Similar to NPS, FMS viral load was highest in early disease and in those with active respiratory symptoms, highlighting the potential role of FMS in understanding infectivity.
BACKGROUND:Human to human transmission of SARS-CoV-2 is driven by the respiratory route but little is known about the pattern and quantity of virus output from exhaled breath. We have previously shown that face-mask sampling (FMS) can detect exhaled tubercle bacilli and have adapted its use to quantify exhaled SARS-CoV-2 RNA in patients admitted to hospital with Coronavirus Disease-2019 (COVID-19). METHODS: Between May and December 2020, we took two concomitant FMS and nasopharyngeal samples (NPS) over two days, starting within 24 h of a routine virus positive NPS in patients hospitalised with COVID-19, at University Hospitals of Leicester NHS Trust, UK. Participants were asked to wear a modified duckbilled facemask for 30 min, followed by a nasopharyngeal swab. Demographic, clinical, and radiological data, as well as International Severe Acute Respiratory and emerging Infections Consortium (ISARIC) mortality and deterioration scores were obtained. Exposed masks were processed by removal, dissolution and analysis of sampling matrix strips fixed within the mask by RT-qPCR. Viral genome copy numbers were determined and results classified as Negative; Low: ≤999 copies; Medium: 1000-99,999 copies and High ≥ 100,000 copies per strip for FMS or per 100 µl for NPS. RESULTS: 102 FMS and NPS were collected from 66 routinely positive patients; median age: 61 (IQR 49 - 77), of which FMS was positive in 38% of individuals and concomitant NPS was positive in 50%. Positive FMS viral loads varied over five orders of magnitude (<10-3.3 x 106 genome copies/strip); 21 (32%) patients were asymptomatic at the time of sampling. High FMS viral load was associated with respiratory symptoms at time of sampling and shorter interval between sampling and symptom onset (FMS High: median (IQR) 2 days (2-3) vs FMS Negative: 7 days (7-10), p = 0.002). On multivariable linear regression analysis, higher FMS viral loads were associated with higher ISARIC mortality (Medium FMS vs Negative FMS gave an adjusted coefficient of 15.7, 95% CI 3.7-27.7, p = 0.01) and deterioration scores (High FMS vs Negative FMS gave an adjusted coefficient of 37.6, 95% CI 14.0 to 61.3, p = 0.002), while NPS viral loads showed no significant association. CONCLUSION: We demonstrate a simple and effective method for detecting and quantifying exhaled SARS-CoV-2 in hospitalised patients with COVID-19. Higher FMS viral loads were more likely to be associated with developing severe disease compared to NPS viral loads. Similar to NPS, FMS viral load was highest in early disease and in those with active respiratory symptoms, highlighting the potential role of FMS in understanding infectivity.
Authors: A Trajman; I Felker; L C Alves; I Coutinho; M Osman; S-A Meehan; U B Singh; Y Schwartz Journal: Int J Tuberc Lung Dis Date: 2022-08-01 Impact factor: 3.427
Authors: Daniel Pan; Shirley Sze; Shalin Abraham; Caroline M Williams; Julian W Tang; Mike R Barer; Manish Pareek Journal: Lancet Microbe Date: 2021-05-12
Authors: Renu Verma; Eugene Kim; Nicholas Degner; Katharine S Walter; Upinder Singh; Jason R Andrews Journal: Open Forum Infect Dis Date: 2021-12-01 Impact factor: 3.835
Authors: Vanessa Schorer; Julian Haas; Robert Stach; Vjekoslav Kokoric; Rüdiger Groß; Jan Muench; Tim Hummel; Harald Sobek; Jan Mennig; Boris Mizaikoff Journal: Sci Rep Date: 2022-02-10 Impact factor: 4.379
Authors: Tyler J Johnson; Robert T Nishida; Ashlesha P Sonpar; Yi-Chan James Lin; Kimberley A Watson; Stephanie W Smith; John M Conly; David H Evans; Jason S Olfert Journal: Sci Rep Date: 2022-03-03 Impact factor: 4.379
Authors: Dorothy Hui Lin Ng; Mei Yi Sim; Hong Hong Huang; Jean Xiang Ying Sim; Jenny Guek Hong Low; Jay Kheng Sit Lim Journal: Eur J Clin Microbiol Infect Dis Date: 2021-07-05 Impact factor: 3.267
Authors: Agnieszka Smolinska; David S Jessop; Kirk L Pappan; Alexandra De Saedeleer; Amerjit Kang; Alexandra L Martin; Max Allsworth; Charlotte Tyson; Martine P Bos; Matt Clancy; Mike Morel; Tony Cooke; Tom Dymond; Claire Harris; Jacqui Galloway; Paul Bresser; Nynke Dijkstra; Viresh Jagesar; Paul H M Savelkoul; Erik V H Beuken; Wesley H V Nix; Renaud Louis; Muriel Delvaux; Doriane Calmes; Benoit Ernst; Simona Pollini; Anna Peired; Julien Guiot; Sara Tomassetti; Andries E Budding; Frank McCaughan; Stefan J Marciniak; Marc P van der Schee Journal: Sci Rep Date: 2021-06-29 Impact factor: 4.379