Hayley Colton1,2, David Hodgson3, Hailey Hornsby2, Rebecca Brown2, Joanne Mckenzie2, Kirsty L Bradley2, Cameron James2, Benjamin B Lindsey1,2, Sarah Birch4, Louise Marsh4, Steven Wood5, Martin Bayley5, Gary Dickson5, David C James6, Martin J Nicklin2, Jon R Sayers2,7,8, Domen Zafred2, Sarah L Rowland-Jones1,2,7, Goura Kudesia9, Adam Kucharski3, Thomas C Darton1,2,7, Thushan I de Silva1,2,7, Paul J Collini1,2,7. 1. South Yorkshire Regional Department of Infection and Tropical Medicine, Sheffield Teaching Hospitals Nhs Foundation Trust, Sheffield, S10 2JF, UK. 2. Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, S10 2TN, UK. 3. Centre for Mathematical Modelling of Infectious Diseases, London School of Hygiene and Tropical Medicine, London, WC1E 7HT, UK. 4. Academic Directorate of Communicable Diseases and Specialised Medicine, Sheffield Teaching Hospitals Nhs Foundation Trust, Sheffield, S10 2JF, UK. 5. Department of Scientific Computing and Informatics, Sheffield Teaching Hospitals Nhs Foundation Trust, Sheffield, S10 2JF, UK. 6. Department of Chemical and Biological Engineering, University of Sheffield, Sheffield, S10 2TN, UK. 7. The Florey Institute for Host-Pathogen Interactions, University of Sheffield, Sheffield, S10 2TN, UK. 8. Sheffield Institute for Nucleic Acids, University of Sheffield, Sheffield, S10 2TN, UK. 9. Department of Virology, Sheffield Teaching Hospitals Nhs Foundation Trust, Sheffield, S5 7AU, UK.
Abstract
Background: We aimed to measure SARS-CoV-2 seroprevalence in a cohort of healthcare workers (HCWs) during the first UK wave of the COVID-19 pandemic, explore risk factors associated with infection, and investigate the impact of antibody titres on assay sensitivity. Methods: HCWs at Sheffield Teaching Hospitals NHS Foundation Trust were prospectively enrolled and sampled at two time points. We developed an in-house ELISA for testing participant serum for SARS-CoV-2 IgG and IgA reactivity against Spike and Nucleoprotein. Data were analysed using three statistical models: a seroprevalence model, an antibody kinetics model, and a heterogeneous sensitivity model. Results: Our in-house assay had a sensitivity of 99·47% and specificity of 99·56%. We found that 24·4% (n=311/1275) of HCWs were seropositive as of 12th June 2020. Of these, 39·2% (n=122/311) were asymptomatic. The highest adjusted seroprevalence was measured in HCWs on the Acute Medical Unit (41·1%, 95% CrI 30·0-52·9) and in Physiotherapists and Occupational Therapists (39·2%, 95% CrI 24·4-56·5). Older age groups showed overall higher median antibody titres. Further modelling suggests that, for a serological assay with an overall sensitivity of 80%, antibody titres may be markedly affected by differences in age, with sensitivity estimates of 89% in those over 60 years but 61% in those ≤30 years. Conclusions: HCWs in acute medical units and those working closely with COVID-19 patients were at highest risk of infection, though whether these are infections acquired from patients or other staff is unknown. Current serological assays may underestimate seroprevalence in younger age groups if validated using sera from older and/or more severe COVID-19 cases. Copyright:
Background: We aimed to measure SARS-CoV-2 seroprevalence in a cohort of healthcare workers (HCWs) during the first UK wave of the COVID-19 pandemic, explore risk factors associated with infection, and investigate the impact of antibody titres on assay sensitivity. Methods: HCWs at Sheffield Teaching Hospitals NHS Foundation Trust were prospectively enrolled and sampled at two time points. We developed an in-house ELISA for testing participant serum for SARS-CoV-2 IgG and IgA reactivity against Spike and Nucleoprotein. Data were analysed using three statistical models: a seroprevalence model, an antibody kinetics model, and a heterogeneous sensitivity model. Results: Our in-house assay had a sensitivity of 99·47% and specificity of 99·56%. We found that 24·4% (n=311/1275) of HCWs were seropositive as of 12th June 2020. Of these, 39·2% (n=122/311) were asymptomatic. The highest adjusted seroprevalence was measured in HCWs on the Acute Medical Unit (41·1%, 95% CrI 30·0-52·9) and in Physiotherapists and Occupational Therapists (39·2%, 95% CrI 24·4-56·5). Older age groups showed overall higher median antibody titres. Further modelling suggests that, for a serological assay with an overall sensitivity of 80%, antibody titres may be markedly affected by differences in age, with sensitivity estimates of 89% in those over 60 years but 61% in those ≤30 years. Conclusions: HCWs in acute medical units and those working closely with COVID-19 patients were at highest risk of infection, though whether these are infections acquired from patients or other staff is unknown. Current serological assays may underestimate seroprevalence in younger age groups if validated using sera from older and/or more severe COVID-19 cases. Copyright:
Authors: Yusuf B Johari; Stephen R P Jaffé; Joseph M Scarrott; Abayomi O Johnson; Théo Mozzanino; Thilo H Pohle; Sheetal Maisuria; Amina Bhayat-Cammack; Giulia Lambiase; Adam J Brown; Kang Lan Tee; Philip J Jackson; Tuck Seng Wong; Mark J Dickman; Ravishankar B Sargur; David C James Journal: Biotechnol Bioeng Date: 2020-11-11 Impact factor: 4.530
Authors: Fatima Amanat; Daniel Stadlbauer; Shirin Strohmeier; Thi H O Nguyen; Veronika Chromikova; Meagan McMahon; Kaijun Jiang; Guha Asthagiri Arunkumar; Denise Jurczyszak; Jose Polanco; Maria Bermudez-Gonzalez; Giulio Kleiner; Teresa Aydillo; Lisa Miorin; Daniel S Fierer; Luz Amarilis Lugo; Erna Milunka Kojic; Jonathan Stoever; Sean T H Liu; Charlotte Cunningham-Rundles; Philip L Felgner; Thomas Moran; Adolfo García-Sastre; Daniel Caplivski; Allen C Cheng; Katherine Kedzierska; Olli Vapalahti; Jussi M Hepojoki; Viviana Simon; Florian Krammer Journal: Nat Med Date: 2020-05-12 Impact factor: 53.440
Authors: Seth Flaxman; Swapnil Mishra; Axel Gandy; H Juliette T Unwin; Thomas A Mellan; Helen Coupland; Charles Whittaker; Harrison Zhu; Tresnia Berah; Jeffrey W Eaton; Mélodie Monod; Azra C Ghani; Christl A Donnelly; Steven Riley; Michaela A C Vollmer; Neil M Ferguson; Lucy C Okell; Samir Bhatt Journal: Nature Date: 2020-06-08 Impact factor: 49.962
Authors: Miriam Mutambudzi; Claire Niedwiedz; Srinivasa Vittal Katikireddi; Evangelia Demou; Ewan Beaton Macdonald; Alastair Leyland; Frances Mair; Jana Anderson; Carlos Celis-Morales; John Cleland; John Forbes; Jason Gill; Claire Hastie; Frederick Ho; Bhautesh Jani; Daniel F Mackay; Barbara Nicholl; Catherine O'Donnell; Naveed Sattar; Paul Welsh; Jill P Pell Journal: Occup Environ Med Date: 2020-12-09 Impact factor: 4.948
Authors: Wilfredo F Garcia-Beltran; Evan C Lam; Michael G Astudillo; Diane Yang; Tyler E Miller; Jared Feldman; Blake M Hauser; Timothy M Caradonna; Kiera L Clayton; Adam D Nitido; Mandakolathur R Murali; Galit Alter; Richelle C Charles; Anand Dighe; John A Branda; Jochen K Lennerz; Daniel Lingwood; Aaron G Schmidt; A John Iafrate; Alejandro B Balazs Journal: Cell Date: 2020-12-15 Impact factor: 41.582
Authors: Tim A Bruckner; Daniel M Parker; Scott M Bartell; Veronica M Vieira; Saahir Khan; Andrew Noymer; Emily Drum; Bruce Albala; Matthew Zahn; Bernadette Boden-Albala Journal: Sci Rep Date: 2021-02-04 Impact factor: 4.379
Authors: Catherine F Houlihan; Nina Vora; Thomas Byrne; Dan Lewer; Gavin Kelly; Judith Heaney; Sonia Gandhi; Moira J Spyer; Rupert Beale; Peter Cherepanov; David Moore; Richard Gilson; Steve Gamblin; George Kassiotis; Laura E McCoy; Charles Swanton; Andrew Hayward; Eleni Nastouli Journal: Lancet Date: 2020-07-09 Impact factor: 79.321
Authors: Adrian Shields; Sian E Faustini; Marisol Perez-Toledo; Sian Jossi; Erin Aldera; Joel D Allen; Saly Al-Taei; Claire Backhouse; Andrew Bosworth; Lyndsey A Dunbar; Daniel Ebanks; Beena Emmanuel; Mark Garvey; Joanna Gray; I Michael Kidd; Golaleh McGinnell; Dee E McLoughlin; Gabriella Morley; Joanna O'Neill; Danai Papakonstantinou; Oliver Pickles; Charlotte Poxon; Megan Richter; Eloise M Walker; Kasun Wanigasooriya; Yasunori Watanabe; Celina Whalley; Agnieszka E Zielinska; Max Crispin; David C Wraith; Andrew D Beggs; Adam F Cunningham; Mark T Drayson; Alex G Richter Journal: Thorax Date: 2020-09-11 Impact factor: 9.139