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1. SARS-CoV-2 B.1.617.2 Delta variant replication and immune evasion

Author

Mlcochova, Petra, Kemp, Steven A., Dhar, Mahesh Shanker, Papa, Guido, Meng, Bo, Ferreira, Isabella A. T. M., Datir, Rawlings, Collier, Dami A., Albecka, Anna, Singh, Sujeet, Pandey, Rajesh, Brown, Jonathan, Zhou, Jie, Goonawardane, Niluka, Mishra, Swapnil, Whittaker, Charles, Mellan, Thomas, Marwal, Robin, Datta, Meena, Sengupta, Shantanu, Ponnusamy, Kalaiarasan, Radhakrishnan, Venkatraman Srinivasan, Abdullahi, Adam, Charles, Oscar, Chattopadhyay, Partha, Devi, Priti, Caputo, Daniela, Peacock, Tom, Wattal, Chand, Goel, Neeraj, Satwik, Ambrish, Vaishya, Raju, Agarwal, Meenakshi, Chauhan, Himanshu, Dikid, Tanzin, Gogia, Hema, Lall, Hemlata, Verma, Kaptan, Singh, Manoj K., Soni, Namita, Meena, Namonarayan, Madan, Preeti, Singh, Priyanka, Sharma, Ramesh, Sharma, Rajeev, Kabra, Sandhya, Kumar, Sattender, Kumari, Swati, Sharma, Uma, Chaudhary, Urmila, Sivasubbu, Sridhar, Scaria, Vinod, Oberoi, J. K., Raveendran, Reena, Datta, S., Das, Saumitra, Maitra, Arindam, Chinnaswamy, Sreedhar, Biswas, Nidhan Kumar, Parida, Ajay, Raghav, Sunil K., Prasad, Punit, Sarin, Apurva, Mayor, Satyajit, Ramakrishnan, Uma, Palakodeti, Dasaradhi, Seshasayee, Aswin Sai Narain, Thangaraj, K., Bashyam, Murali Dharan, Dalal, Ashwin, Bhat, Manoj, Shouche, Yogesh, Pillai, Ajay, Abraham, Priya, Potdar, Varsha Atul, Cherian, Sarah S., Desai, Anita Sudhir, Pattabiraman, Chitra, Manjunatha, M. V., Mani, Reeta S., Udupi, Gautam Arunachal, Nandicoori, Vinay, Tallapaka, Karthik Bharadwaj, Sowpati, Divya Tej, Kawabata, Ryoko, Morizako, Nanami, Sadamasu, Kenji, Asakura, Hiroyuki, Nagashima, Mami, Yoshimura, Kazuhisa, Ito, Jumpei, Kimura, Izumi, Uriu, Keiya, Kosugi, Yusuke, Suganami, Mai, Oide, Akiko, Yokoyama, Miyabishara, Chiba, Mika, Saito, Akatsuki, Butlertanaka, Erika P., Tanaka, Yuri L., Ikeda, Terumasa, Motozono, Chihiro, Nasser, Hesham, Shimizu, Ryo, Yuan, Yue, Kitazato, Kazuko, Hasebe, Haruyo, Nakagawa, So, Wu, Jiaqi, Takahashi, Miyoko, Fukuhara, Takasuke, Shimizu, Kenta, Tsushima, Kana, Kubo, Haruko, Shirakawa, Kotaro, Kazuma, Yasuhiro, Nomura, Ryosuke, Horisawa, Yoshihito, Takaori-Kondo, Akifumi, Tokunaga, Kenzo, Ozono, Seiya, Baker, Stephen, Dougan, Gordon, Hess, Christoph, Kingston, Nathalie, Lehner, Paul J., Lyons, Paul A., Matheson, Nicholas J., Owehand, Willem H., Saunders, Caroline, Summers, Charlotte, Thaventhiran, James E. D., Toshner, Mark, Weekes, Michael P., Maxwell, Patrick, Shaw, Ashley, Bucke, Ashlea, Calder, Jo, Canna, Laura, Domingo, Jason, Elmer, Anne, Fuller, Stewart, Harris, Julie, Hewitt, Sarah, Kennet, Jane, Jose, Sherly, Kourampa, Jenny, Meadows, Anne, O'Brien, Criona, Price, Jane, Publico, Cherry, Rastall, Rebecca, Ribeiro, Carla, Rowlands, Jane, Ruffolo, Valentina, Tordesillas, Hugo, Bullman, Ben, Dunmore, Benjamin J., Fawke, Stuart, Graf, Stefan, Hodgson, Josh, Huang, Christopher, Hunter, Kelvin, Jones, Emma, Legchenko, Ekaterina, Matara, Cecilia, Martin, Jennifer, Mescia, Federica, O'Donnell, Ciara, Pointon, Linda, Pond, Nicole, Shih, Joy, Sutcliffe, Rachel, Tilly, Tobias, Treacy, Carmen, Tong, Zhen, Wood, Jennifer, Wylot, Marta, Bergamaschi, Laura, Betancourt, Ariana, Bower, Georgie, Cossetti, Chiara, De Sa, Aloka, Epping, Madeline, Gleadall, Nick, Grenfell, Richard, Hinch, Andrew, Huhn, Oisin, Jackson, Sarah, Jarvis, Isobel, Krishna, Ben, Lewis, Daniel, Marsden, Joe, Nice, Francesca, Okecha, Georgina, Omarjee, Ommar, Perera, Marianne, Potts, Martin, Richoz, Nathan, Romashova, Veronika, Yarkoni, Natalia Savinykh, Sharma, Rahul, Stefanucci, Luca, Stephens, Jonathan, Strezlecki, Mateusz, Turner, Lori, De Bie, Eckart M. D. D., Bunclark, Katherine, Josipovic, Masa, Mackay, Michael, Rossi, Sabrina, Selvan, Mayurun, Spencer, Sarah, Yong, Cissy, Allison, John, Butcher, Helen, Clapham-Riley, Debbie, Dewhurst, Eleanor, Furlong, Anita, Graves, Barbara, Gray, Jennifer, Ivers, Tasmin, Kasanicki, Mary, Le Gresley, Emma, Linger, Rachel, Meloy, Sarah, Muldoon, Francesca, Ovington, Nigel, Papadia, Sofia, Phelan, Isabel, Stark, Hannah, Stirrups, Kathleen E., Townsend, Paul, Walker, Neil, Webster, Jennifer, Scholtes, Ingrid, Hein, Sabine, King, Rebecca, Mavousian, Antranik, Lee, Joo Hyeon, Bassi, Jessica, Silacci-Fegni, Chiara, Saliba, Christian, Pinto, Dora, Irie, Takashi, Yoshida, Isao, Hamilton, William L., Sato, Kei, Bhatt, Samir, Flaxman, Seth, James, Leo C., Corti, Davide, Piccoli, Luca, Barclay, Wendy S., Rakshit, Partha, Agrawal, Anurag, Gupta, Ravindra K., (INSACOG), Indian SARS-CoV-2 Genomics Consortium, Consortium, Genotype to Phenotype Japan (G2P-Japan), Collaboration, CITIID-NIHR BioResource COVID-19, Gupta, Ravindra K [0000-0001-9751-1808], Apollo - University of Cambridge Repository, and Gupta, Ravindra K. [0000-0001-9751-1808]

Subjects
Male, COVID-19 Vaccines, medicine.drug_class, Health Personnel, India, Monoclonal antibody, Virus Replication, Antibodies, Cell Line, Cell Fusion, Immune system, 13/100, medicine, Humans, Neutralizing antibody, Antibodies, Neutralizing, Female, Kinetics, SARS-CoV-2, Spike Glycoprotein, Coronavirus, Vaccination, Immune Evasion, Neutralizing, 631/326/596/4130, Syncytium, Multidisciplinary, Cell fusion, biology, article, Vaccine efficacy, 631/250/254, Virology, Spike Glycoprotein, Coronavirus, 13/31, biology.protein, Antibody, Infection
Abstract

The B.1.617.2 (Delta) variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first identified in the state of Maharashtra in late 2020 and spread throughout India, outcompeting pre-existing lineages including B.1.617.1 (Kappa) and B.1.1.7 (Alpha)1. In vitro, B.1.617.2 is sixfold less sensitive to serum neutralizing antibodies from recovered individuals, and eightfold less sensitive to vaccine-elicited antibodies, compared with wild-type Wuhan-1 bearing D614G. Serum neutralizing titres against B.1.617.2 were lower in ChAdOx1 vaccinees than in BNT162b2 vaccinees. B.1.617.2 spike pseudotyped viruses exhibited compromised sensitivity to monoclonal antibodies to the receptor-binding domain and the amino-terminal domain. B.1.617.2 demonstrated higher replication efficiency than B.1.1.7 in both airway organoid and human airway epithelial systems, associated with B.1.617.2 spike being in a predominantly cleaved state compared with B.1.1.7 spike. The B.1.617.2 spike protein was able to mediate highly efficient syncytium formation that was less sensitive to inhibition by neutralizing antibody, compared with that of wild-type spike. We also observed that B.1.617.2 had higher replication and spike-mediated entry than B.1.617.1, potentially explaining the B.1.617.2 dominance. In an analysis of more than 130 SARS-CoV-2-infected health care workers across three centres in India during a period of mixed lineage circulation, we observed reduced ChAdOx1 vaccine effectiveness against B.1.617.2 relative to non-B.1.617.2, with the caveat of possible residual confounding. Compromised vaccine efficacy against the highly fit and immune-evasive B.1.617.2 Delta variant warrants continued infection control measures in the post-vaccination era., A study of SARS-CoV-2 variants examining their transmission, infectivity, and potential resistance to therapies provides insights into the biology of the Delta variant and its role in the global pandemic.

Published
2022
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2. Screening of healthcare workers for SARS-CoV-2 highlights the role of asymptomatic carriage in COVID-19 transmission

Author

Rivett, Lucy, Sridhar, Sushmita, Sparkes, Dominic, Routledge, Matthew, Jones, Nick K, Forrest, Sally, Young, Jamie, Pereira-Dias, Joana, Hamilton, William L, Ferris, Mark, Torok, M Estee, Meredith, Luke, Collaboration, The CITIID-NIHR COVID-19 BioResource, Curran, Martin D, Fuller, Stewart, Chaudhry, Afzal, Shaw, Ashley, Samworth, Richard J, Bradley, John R, Dougan, Gordon, Smith, Kenneth GC, Lehner, Paul J, Matheson, Nicholas J, Wright, Giles, Goodfellow, Ian G, Baker, Stephen, Weekes, Michael P, Gupta, Ravi, Lyons, Paul A, Toshner, Mark, Warne, Ben, Bartholdson Scott, Josefin, Cormie, Claire, Gill, Harmeet, Kean, Iain, Maes, Mailis, Reynolds, Nicola, Wantoch, Michelle, Caddy, Sarah, Caller, Laura, Feltwell, Theresa, Hall, Grant, Hosmillo, Myra, Houldcroft, Charlotte, Jahun, Aminu, Khokhar, Fahad, Yakovleva, Anna, Butcher, Helen, Caputo, Daniela, Clapham-Riley, Debra, Dolling, Helen, Furlong, Anita, Graves, Barbara, Gresley, Emma Le, Kingston, Nathalie, Papadia, Sofia, Stark, Hannah, Stirrups, Kathleen E, Webster, Jennifer, Calder, Joanna, Harris, Julie, Hewitt, Sarah, Kennet, Jane, Meadows, Anne, Rastall, Rebecca, Brien, Criona O, Price, Jo, Publico, Cherry, Rowlands, Jane, Ruffolo, Valentina, Tordesillas, Hugo, Brookes, Karen, Canna, Laura, Cruz, Isabel, Dempsey, Katie, Elmer, Anne, Escoffery, Naidine, Jones, Heather, Ribeiro, Carla, Saunders, Caroline, Wright, Angela, Nyagumbo, Rutendo, Roberts, Anne, Bucke, Ashlea, Hargreaves, Simone, Johnson, Danielle, Narcorda, Aileen, Read, Debbie, Sparke, Christian, Warboys, Lucy, Lagadu, Kirsty, Mactavous, Lenette, Gould, Tim, Raine, Tim, Mather, Claire, Ramenatte, Nicola, Vallier, Anne-Laure, Kasanicki, Mary, Eames, Penelope-Jane, McNicholas, Chris, Thake, Lisa, Bartholomew, Neil, Brown, Nick, Parmar, Surendra, Zhang, Hongyi, Bowring, Ailsa, Martell, Geraldine, Quinnell, Natalie, Wright, Jo, Murphy, Helen, Dunmore, Benjamin J, Legchenko, Ekaterina, Gräf, Stefan, Huang, Christopher, Hodgson, Josh, Hunter, Kelvin, Martin, Jennifer, Mescia, Federica, O'Donnell, Ciara, Pointon, Linda, Shih, Joy, Sutcliffe, Rachel, Tilly, Tobias, Tong, Zhen, Treacy, Carmen, Wood, Jennifer, Bergamaschi, Laura, Betancourt, Ariana, Bowyer, Georgie, De Sa, Aloka, Epping, Maddie, Hinch, Andrew, Huhn, Oisin, Jarvis, Isobel, Lewis, Daniel, Marsden, Joe, McCallum, Simon, Nice, Francescsa, Rivett, Lucy [0000-0002-2781-9345], Lehner, Paul J [0000-0001-9383-1054], Matheson, Nicholas J [0000-0002-3318-1851], Goodfellow, Ian G [0000-0002-9483-510X], Weekes, Michael P [0000-0003-3196-5545], and Apollo - University of Cambridge Repository

Subjects
Epidemiology and Global Health, SARS-CoV-2, infectious disease, education, occupational health, virus diseases, COVID-19, Human Biology and Medicine, Research Article, virology, emerging pathogens, Human, Virus
Abstract

Funder: Addenbrooke's Charitable Trust, Cambridge University Hospitals; FundRef: http://dx.doi.org/10.13039/501100002927, Significant differences exist in the availability of healthcare worker (HCW) SARS-CoV-2 testing between countries, and existing programmes focus on screening symptomatic rather than asymptomatic staff. Over a 3 week period (April 2020), 1032 asymptomatic HCWs were screened for SARS-CoV-2 in a large UK teaching hospital. Symptomatic staff and symptomatic household contacts were additionally tested. Real-time RT-PCR was used to detect viral RNA from a throat+nose self-swab. 3% of HCWs in the asymptomatic screening group tested positive for SARS-CoV-2. 17/30 (57%) were truly asymptomatic/pauci-symptomatic. 12/30 (40%) had experienced symptoms compatible with coronavirus disease 2019 (COVID-19)>7 days prior to testing, most self-isolating, returning well. Clusters of HCW infection were discovered on two independent wards. Viral genome sequencing showed that the majority of HCWs had the dominant lineage B∙1. Our data demonstrates the utility of comprehensive screening of HCWs with minimal or no symptoms. This approach will be critical for protecting patients and hospital staff.

Published
2020
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3. Effective control of SARS-CoV-2 transmission between healthcare workers during a period of diminished community prevalence of COVID-19

Author

Jones, Nick K, Rivett, Lucy, Sparkes, Dominic, Forrest, Sally, Sridhar, Sushmita, Young, Jamie, Pereira-Dias, Joana, Cormie, Claire, Gill, Harmeet, Reynolds, Nicola, Wantoch, Michelle, Routledge, Matthew, Warne, Ben, Levy, Jack, Córdova Jiménez, William David, Samad, Fathima Nisha Begum, McNicholas, Chris, Ferris, Mark, Gray, Jane, Gill, Michael, Collaboration, The CITIID-NIHR COVID-19 BioResource, Curran, Martin D, Fuller, Stewart, Chaudhry, Afzal, Shaw, Ashley, Bradley, John R, Hannon, Gregory J, Goodfellow, Ian G, Dougan, Gordon, Smith, Kenneth GC, Wright, Giles, Baker, Stephen, Weekes, Michael P, Bradley, John, Goodfellow, Ian, Gupta, Ravi, Lehner, Paul J, Lyons, Paul A, Matheson, Nicholas J, Torok, M Estee, Toshner, Mark, Jones, Nick K [0000-0003-4475-7761], Sridhar, Sushmita [0000-0001-7453-7482], Hannon, Gregory J [0000-0003-4021-3898], Goodfellow, Ian G [0000-0002-9483-510X], Lehner, Paul J [0000-0001-9383-1054], Matheson, Nicholas J [0000-0002-3318-1851], Weekes, Michael P [0000-0003-3196-5545], and Apollo - University of Cambridge Repository

Subjects
Epidemiology and Global Health, SARS-CoV-2, infectious disease, occupational health, virus diseases, COVID-19, Research Advance, Human Biology and Medicine, virology, emerging pathogens, Human
Abstract

Funder: Addenbrooke's Charitable Trust, Cambridge University Hospitals; FundRef: http://dx.doi.org/10.13039/501100002927, Funder: National Institute for Health Research; FundRef: http://dx.doi.org/10.13039/501100000272, Previously, we showed that 3% (31/1032)of asymptomatic healthcare workers (HCWs) from a large teaching hospital in Cambridge, UK, tested positive for SARS-CoV-2 in April 2020. About 15% (26/169) HCWs with symptoms of coronavirus disease 2019 (COVID-19) also tested positive for SARS-CoV-2 (Rivett et al., 2020). Here, we show that the proportion of both asymptomatic and symptomatic HCWs testing positive for SARS-CoV-2 rapidly declined to near-zero between 25th April and 24th May 2020, corresponding to a decline in patient admissions with COVID-19 during the ongoing UK ‘lockdown’. These data demonstrate how infection prevention and control measures including staff testing may help prevent hospitals from becoming independent ‘hubs’ of SARS-CoV-2 transmission, and illustrate how, with appropriate precautions, organizations in other sectors may be able to resume on-site work safely.

Published
2020

4. Effective control of SARS-CoV-2 transmission between healthcare workers during a period of diminished community prevalence of COVID-19

Author

Jones, Nick K, Rivett, Lucy, Sparkes, Dominic, Forrest, Sally, Sridhar, Sushmita, Young, Jamie, Pereira-Dias, Joana, Cormie, Claire, Gill, Harmeet, Reynolds, Nicola, Wantoch, Michelle, Routledge, Matthew, Warne, Ben, Levy, Jack, Córdova Jiménez, William David, Samad, Fathima Nisha Begum, McNicholas, Chris, Ferris, Mark, Gray, Jane, Gill, Michael, CITIID-NIHR COVID-19 BioResource Collaboration, Curran, Martin D, Fuller, Stewart, Chaudhry, Afzal, Shaw, Ashley, Bradley, John R, Hannon, Gregory J, Goodfellow, Ian G, Dougan, Gordon, Smith, Kenneth Gc, Lehner, Paul J, Wright, Giles, Matheson, Nicholas J, Baker, Stephen, and Weekes, Michael P

Subjects
Adult, Male, medicine, Infectious Disease Transmission, Patient-to-Professional, infectious disease, Health Personnel, Pneumonia, Viral, global health, Real-Time Polymerase Chain Reaction, Hospitals, University, Betacoronavirus, COVID-19 Testing, Patient Admission, Nasopharynx, Disease Transmission, Infectious, Prevalence, Humans, Mass Screening, human, Hospitals, Teaching, Pandemics, emerging pathogens, Family Characteristics, Infection Control, SARS-CoV-2, Clinical Laboratory Techniques, virus diseases, COVID-19, human biology, Middle Aged, 3. Good health, virology, Community-Acquired Infections, Occupational Diseases, England, occupational health, Asymptomatic Diseases, epidemiology, Female, Contact Tracing, Symptom Assessment, Coronavirus Infections, Hospital Units, Program Evaluation
Abstract

Previously, we showed that 3% (31/1032)of asymptomatic healthcare workers (HCWs) from a large teaching hospital in Cambridge, UK, tested positive for SARS-CoV-2 in April 2020. About 15% (26/169) HCWs with symptoms of coronavirus disease 2019 (COVID-19) also tested positive for SARS-CoV-2 (Rivett et al., 2020). Here, we show that the proportion of both asymptomatic and symptomatic HCWs testing positive for SARS-CoV-2 rapidly declined to near-zero between 25th April and 24th May 2020, corresponding to a decline in patient admissions with COVID-19 during the ongoing UK 'lockdown'. These data demonstrate how infection prevention and control measures including staff testing may help prevent hospitals from becoming independent 'hubs' of SARS-CoV-2 transmission, and illustrate how, with appropriate precautions, organizations in other sectors may be able to resume on-site work safely.

5. Screening of healthcare workers for SARS-CoV-2 highlights the role of asymptomatic carriage in COVID-19 transmission

Author

Rivett, Lucy, Sridhar, Sushmita, Sparkes, Dominic, Routledge, Matthew, Jones, Nick K, Forrest, Sally, Young, Jamie, Pereira-Dias, Joana, Hamilton, William L, Ferris, Mark, Torok, M Estee, Meredith, Luke, CITIID-NIHR COVID-19 BioResource Collaboration, Curran, Martin D, Fuller, Stewart, Chaudhry, Afzal, Shaw, Ashley, Samworth, Richard J, Bradley, John R, Dougan, Gordon, Smith, Kenneth Gc, Lehner, Paul J, Matheson, Nicholas J, Wright, Giles, Goodfellow, Ian G, Baker, Stephen, and Weekes, Michael P

Subjects
Male, medicine, COVID-19 Vaccines, infectious disease, Health Personnel, education, Pneumonia, Viral, global health, virus, Real-Time Polymerase Chain Reaction, Betacoronavirus, COVID-19 Testing, Humans, human, Asymptomatic Infections, Pandemics, emerging pathogens, Infection Control, SARS-CoV-2, Clinical Laboratory Techniques, virus diseases, COVID-19, human biology, United Kingdom, 3. Good health, virology, occupational health, epidemiology, Female, Coronavirus Infections
Abstract

Significant differences exist in the availability of healthcare worker (HCW) SARS-CoV-2 testing between countries, and existing programmes focus on screening symptomatic rather than asymptomatic staff. Over a 3 week period (April 2020), 1032 asymptomatic HCWs were screened for SARS-CoV-2 in a large UK teaching hospital. Symptomatic staff and symptomatic household contacts were additionally tested. Real-time RT-PCR was used to detect viral RNA from a throat+nose self-swab. 3% of HCWs in the asymptomatic screening group tested positive for SARS-CoV-2. 17/30 (57%) were truly asymptomatic/pauci-symptomatic. 12/30 (40%) had experienced symptoms compatible with coronavirus disease 2019 (COVID-19)>7 days prior to testing, most self-isolating, returning well. Clusters of HCW infection were discovered on two independent wards. Viral genome sequencing showed that the majority of HCWs had the dominant lineage B∙1. Our data demonstrates the utility of comprehensive screening of HCWs with minimal or no symptoms. This approach will be critical for protecting patients and hospital staff.

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