Adaptive immunity to SARS-CoV-2 in cancer patients: The CAPTURE study

TL;DR: A longitudinal cohort study of cancer patients and healthcare workers (HCWs) integrating longitudinal immune profiling and clinical annotation was conducted in this article, where SARS-CoV-2-specific T-cell responses were detected, and CD4+ T-cells responses correlated with S1 antibody levels.

Abstract: SUMMARY There is a pressing need to characterise the nature, extent and duration of immune response to SARS-CoV-2 in cancer patients and inform risk-reduction strategies and preserve cancer outcomes. CAPTURE is a prospective, longitudinal cohort study of cancer patients and healthcare workers (HCWs) integrating longitudinal immune profiling and clinical annotation. We evaluated 529 blood samples and 1051 oronasopharyngeal swabs from 144 cancer patients and 73 HCWs and correlated with >200 clinical variables. In patients with solid cancers and HCWs, S1-reactive and neutralising antibodies to SARS-CoV-2 were detectable five months post-infection. SARS-CoV-2-specific T-cell responses were detected, and CD4+ T-cell responses correlated with S1 antibody levels. Patients with haematological malignancies had impaired but partially compensated immune responses. Overall, cancer stage, disease status, and therapies did not correlate with immune responses. These findings have implications for understanding individual risks and potential effectiveness of SARS-CoV-2 vaccination in the cancer population.

Summary

INTRODUCTION

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associated with coronavirus disease 2019 (COVID-19) has resulted in a global pandemic with a particularly detrimental impact on cancer patients.
• Next, the authors quantified total S1-reactive antibody titres by ELISA in 144 patients at multiple time points, with at least one sample taken at >25 days after POD .

POD.

• Given that cross-reactivity to seasonal human coronaviruses (Ng et al., 2020) has been reported the authors evaluated matched pre-pandemic sera from 47 patients, 10 with and 37 without S1-reactive antibodies.
• Preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
• Presence of neutralising antibodies did not differ significantly between HCWs with or without symptoms (p = 0.6).
• T-cells was significantly correlated with S1-reactive antibody titres, suggesting the latter may reflect Tfh T-cell activation .

DISCUSSION

• This is the first report from a prospective study of the adaptive immune response to SARSCoV-2 in cancer patients and HCWs.
• Thanks to broad inclusion criteria, enhanced laboratory criteria for case definition, and longitudinal follow up, the authors provide an accurate picture of SARS-CoV-2 status and dynamics of the anti-viral immune response, in the context of clinical presentation of COVID-19 and cancer characteristics.
• Preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
• Most patients with solid malignancies mounted S1-reactive and neutralising antibody responses that appeared stable and comparable to what has been reported in non-cancer populations.
• The authors data so far reflect those who recovered from COVID-19 but included a broad representation of illness from asymptomatic to severe.

ACKNOWLEDGMENTS

• The authors thank the CAPTURE trial team, including Eleanor Carlyle, Kim Edmonds, and Lyra Del Rosario, as well as Somya Agarwal, Hamid Ahmod, Natalie Ash, Ravinder Dhaliwal, Lauren Dowdie, Tara Foley, Lucy Holt, Justine Korteweg, Charlotte Lewis, Karla Lingard, Mary Mangwende, Aida Murra, Kema Peat, Sarah Sarker, Nahid Shaikh, Sarah Vaughan, and Fiona Williams.
• A.F. has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 892360.
• L.A. is funded by the Royal Marsden Cancer Charity.
• For the purpose of Open Access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission.

DECLARATION OF INTERESTS

• S.T. has received speaking fees from Roche, Astra Zeneca, Novartis and Ipsen.
• S.T. has the following patents filed: Indel mutations as a therapeutic target and predictive biomarker PCTGB2018/051892 and PCTGB2018/051893 and Clear Cell Renal Cell Carcinoma Biomarkers P113326GB. C.S. is Royal Society Napier Research Professor (RP150154).
• L.P. has received research funding from Pierre Fabre, and honoria from Pfizer, Ipsen, Bristol-Myers Squibb, and EUSA Pharma.

FIGURE LEGENDS

• CAPTURE recruitment, follow up schedules, sample, and data collection overview, and planned analyses, also known as Figure 1.
• SARS-CoV-2 infection status by RT-PCR and S1-reactive antibodies were analysed at recruitment and in serial samples.
• RTPCR results prior to recruitment were extracted from electronic patient records.
• B) S1-reactive antibody titres across cancer types.
• Dotted lines and grey areas at graph bottom indicate limit of detection.

Admission to hospital

• Preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
• 26 Pneumonia Required corticosteroids (>10 mg equivalent prednisolone).
• Need for mechanical ventilation/NIV Venous thromboembolism 7 16) 5 (10) 3 (7) 1 (2) - - - - - - - - a, Indicates positive/negative for SARS-CoV2 by laboratory definition; b, Expressed as number and percent of affected individuals unless otherwise specified.
• Preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

Materials Availability

• Materials used in this study will be made available upon request.
• There are restrictions to the availability based on limited quantities.

Study design

• CAPTURE is a prospective, longitudinal study, the study design has previously been described in detail (Au, Boos, Swerdlow, Byrne, Shepherd, Fendler and Turajlic, 2020).
• Exploratory endpoints pertain to characterising clinical and immunological determinants of COVID-19 in cancer patients.
• Planned interim analysis took place after 6 months of active recruitment.
• The TRACERx Renal sub-study CAPTURE was submitted as part of Substantial Amendment 9 and approved by London - Fulham Research Ethics Committee on 01/05/2020 and the Health Research Authority on 30/04/2020.
• For healthcare workers, study sampling and self-reported data are collected via an online questionnaire at baseline and repeated 2-4 weekly for three months and 3-monthly thereafter for a follow up period of one year.

Data and Sample Sources

• Patient-reported outcome data are collected using PROFILES (Patient Reported Outcomes Following Initial treatment and Long-term evaluation of Survivorship; https://profilesstudy.rmh.nhs.uk/).
• Online questionnaires for baseline and follow up assessments were designed to record data for cancer patients and healthcare workers participating in CAPTURE.
• Preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
• 29 placement, placement in COVID-19 dedicated area, exposure to aerosols, taking SARS-CoV-2 swabs from patients.
• Surplus serum from patient biochemistry samples taken as part of routine care were also retrieved and linked to the study IDs before anonymisation and study analysis.

Cell lines and viruses

• SUP-T1 cells stably transfected with spike or control vectors were obtained from Martin Pule, and Leila Mekkaoui.
• Vero E6 cells were from the National Institute for Biological Standards and Control, UK.
• The SARS-CoV-2 isolate hCoV-19/England/02/2020 was obtained from the Respiratory Virus Unit, Public Health England, UK, and propagated in Vero E6 cells.

METHOD DETAILS

• Handling of oronasopharyngeal swabs and RNA isolation preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
• 30 SARS-CoV-2 RT-PCR was performed from oronasopharyngeal swabs within the Crick Covid19 testing pipeline (Aitken et al., 2020).
• Oronasopharyngeal swabs were collected in VTM medium, frozen within 24 hrs after collection, and stored at -80ºC until processing.
• RNA isolation was completely automated on a Biomek FX using a kit-free, silica bead-based method.

SARS-CoV-2 RT-PCR

• SARS-CoV-2 RT-PCR was performed using the real-time fluorescent RT-PCR kit for detecting 2019-nCoV (BGI).
• All samples were measured in duplicates on separate plates and an internal control was run for each sample.
• Runs were regarded as valid when negative control Samples with non-exponential amplification were excluded from analysis.
• Preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
• All blood samples and isolated products were handled in a CL2 laboratory inside a biosafety cabinet using appropriate personal protective equipment and safety measures, which were in accordance with a risk assessment and standard operating procedure approved by the safety, health and sustainability committee at the Francis Crick Institute.

Plasma and PBMC isolation

• Whole blood was collected in EDTA tubes (VWR) and stored at 4ºC until processing.
• All samples were processed within 24 hrs.
• Prior to processing tubes were brought to room temperature.
• PBMC and plasma were isolated by density-gradient centrifugation using pre-filled centrifugation tubes .
• The cell layer was then collected and washed twice in PBS by centrifugation for 10 min at 300 xg at room temperature.

Serum isolation

• Whole blood was collected in serum coagulation tubes (Vacuette CAT tubes, Greiner) for serum isolation and stored at 4ºC until processing.
• Fifty microliters of serum were then added to the wells and incubated for 2 hrs at room temperature.
• After washing four times with PBS-T (PBS, 0.05% Tween 20), plates were incubated with alkaline phosphatase-conjugated goat anti-human IgG (1:1000, Jackson ImmunoResearch) for 1 hr. CR3022 (Absolute Antibodies) was used as a positive control.
• Spike-expressing and control SUP-T1 cells were gated and mean fluorescence intensity (MFI) of both populations was measured.

Neutralising antibody assay

• Confluent monolayers of Vero E6 cells were incubated with SARS-CoV-2 virus and twofold serial dilutions of heat-treated serum or plasma samples starting at 1:40 for 4 hrs at 37ºC, 5% CO2, in duplicates.
• The inoculum was then removed, and cells were overlaid with viral growth medium.
• Virus plaques were visualized by immunostaining, as described previously for the neutralisation of influenza viruses using a rabbit polyclonal anti-NSP8 antibody used at 1:1000 dilution and All rights reserved.
• Preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
• 33 anti-rabbit-HRP conjugated antibody at 1:1000 dilution and detected by action of HRP on a tetramethyl benzidine (TMB) based substrate.

T-cell stimulation

• Cells were stimulated with 4 µl/well PepTivator SARS-CoV-2 S, M, or N pools (representing 1µg/ml final concentration per peptide; Miltenyi Biotec, Surrey, UK).
• Staphylococcal enterotoxin B (Merck, UK) was used as a positive control at 0.5µg/ml final concentration, negative control was PBS containing DMSO at 0.002% final concentration.

Activation-induced marker assay

• PBMC supernatants were collected for cytokine analysis after stimulation for 24 hrs.
• A surface staining mix was prepared per well, containing 2 µl/well of each antibody for surface staining (see key resources table for a full list of antibodies) in 50:50 brilliant stain buffer (BD) and FACS buffer.
• Cells were washed once in FACS buffer and fixed in 1% PFA in FACS buffer for 20 min, then washed once and resuspended in 200 µl PBS.
• When S, M, and N stimulation were combined the sum of AIM-positive cells was divided by the three times the percentage of positive cells in the negative control.
• Preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

IFN-y ELISA

• IFN-y ELISA was performed using the human IFN-y DuoSet ELISA (R&D Systems) according to the manufacturer’s instructions.
• Briefly, 96-well plates were coated overnight with capture antibody, washed twice in wash buffer then blocked with reagent diluent for 2 hrs at room temperature.
• Reaction was developed using 200 µl substrate solution for 20 min in the dark at room temperature then stopped with 50 µl stop solution.
• Serial dilutions of standard were run on each plate.
• Concentrations were calculated by linear regression of standard concentrations ranging (0 - 600) pg/ml and normalized to the number of stimulated PBMC.

QUANTIFICATION AND STATISTICAL ANALYSIS

• Statistical details for each experiment are provided in the figure legends.
• Preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
• Bars at the left side represent the frequency of symptoms across all HCWs.

Figure S3: Gating strategies (related to Figure 3,4,5)

• (A) Gating strategy for flow analysis of S-reactive IgG, IgG, IgA. (B) Gating strategy for flow analysis of T-cell activation.
• Preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
• Correlation of humoral and T-cell response with each other and clinical characteristics in cancer patients (A) Correlation matrix of immune response in cancer patients with demographic, COVID-19 severity, and cancer characteristics, also known as 37 Figure S4.
• Correlation of S1-reactive antibody titres with (B) WHO severity score and (C) age.
• P-values < 0.05 were considered significant, significant correlations are indicated by asterisks in the correlation matrix.

Figure S5: Antibody response in HCWs (related to Figure 4)

• T-cell response in cancer patients and HCWs Comparison of CD4+ and CD8+, also known as Figure S6.
• Correlation of S1-reactive antibody titres with Sars-CoV-2-specific (D) CD4+ and (E) CD8+.
• Per patient increase in (I) CD4+ and (J) CD8+ preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.

Figures

Figure 1

Full text

1
Adaptive immunity to SARS-CoV-2 in cancer patients: The
CAPTURE study
Annika Fendler
1,36
, Lewis Au
1,2,36
, Laura Amanda Boos
2,36
, Fiona Byrne
1,36
, Scott T.C.
Shepherd
1,2,36
, Ben Shum
1,2
, Camille L. Gerard
1
, Barry Ward
1
, Wenyi Xie
1
, Maddalena
Cerrone
3
, Georgina H. Cornish
4
, Martin Pule
5,6
, Leila Mekkaoui
6
, Kevin W. Ng
4
, Richard
Stone
7
, Camila Gomes
7
, Helen R. Flynn
8
, Ana Agua-Doce
9
, Phillip Hobson
9
, Simon Caidan
10
,
Mike Howell
11
, Robert Goldstone
11
, Mike Gavrielides
12
, Emma Nye
7
, Bram Snijders
8
, James
Macrae
13
, Jerome Nicod
11
, Adrian Hayday
14
, Firza Gronthoud
15
, Christina Messiou
16
, David
Cunningham
17
, Ian Chau
17
, Naureen Starling
17
, Nicholas Turner
18
, Jennifer Rusby
18
, Liam
Welsh
19
, Nicholas van As
20
, Robin Jones
21
, Joanne Droney
22
, Susana Banerjee
23
, Kate
Tatham
24
, Shaman Jhanji
24
,
Mary O’Brien
25
, Olivia Curtis
25
, Kevin Harrington
26
, Shreerang
Bhide
26
, Tim Slattery
2
, Yasir Khan
2
, Zayd Tippu
2
, Isla Leslie
2
, Spyridon Gennatas
27
, Alicia
Okines
18,27
,
Alison Reid
20
, Kate Young
2
, Andrew Furness
2
, Lisa Pickering
2
,
Sonia Ghandi
28
,
Steve Gamblin
29
, Charles Swanton
30
on behalf of the Crick COVID19 consortium, Emma
Nicholson
31
,
Sacheen Kumar
17
, Nadia Yousaf
25,27
,
Katalin Wilkinson
3
,
Anthony Swerdlow
32
,
Ruth Harvey
33
, George Kassiotis
4
, Robert Wilkinson
3,34,35
, James Larkin
2
, Samra Turajlic
1,2,*
on
behalf of the CAPTURE consortium
1
Cancer Dynamics Laboratory, The Francis Crick Institute, London, NW1 1AT, UK
2
Skin and Renal Units, The Royal Marsden NHS Foundation Trust, London, SW3 6JJ, UK
3
Tuberculosis Laboratory, The Francis Crick Institute, London, NW1 1AT, UK
4
Retroviral Immunology Laboratory, The Francis Crick Institute, London, NW1 1AT, UK
5
Research Department of Haematology at University College L ondon Cancer Institute, WC1E
6DD, London, UK
6
Autolus Limited, The MediaWorks, 191 Wood Lane, London, W12 7F
7
Experimental Histopathology Laboratory, The Francis Crick Institute, London, NW1 1AT, UK
8
Mass Spectrometry Proteomics Science Technology Platform, The Francis Crick Institute,
London, NW1 1AT, UK
9
Flow Cytometry Scientific Technology Platform, The Francis Crick Institute, London, NW1
1AT, UK
10
Safety, Health & Sustainability, The Francis Crick Institute, London, NW1 1AT, UK
11
Advances Sequencing Facility, The Francis Crick Institute, London, NW1 1AT, UK
12
Scientific Computing Scientific Technology Platform, The Francis Crick Institute, London,
NW1 1AT, UK
13
Metabolomics Scientific Technology Platform, The Francis Crick Institute, London, NW1
1AT, UK
14
Immunosurveillance Laboratory, The Francis Crick Institute, London, NW1 1AT, UK
15
Department of Pathology, The Royal Marsden NHS Foundation Trust, London, NW1 1AT,
UK
16
Department of Radiology, The Royal Marsden NHS Foundation Trust, London, SW3 6JJ, UK
17
Gastrointestinal Unit, The Royal Marsden NHS Foundation Trust, London, SW3 6JJ, UK
18
Breast Unit, The Royal Marsden NHS Foundation Trust, London, SW3 6JJ, UK
19
Neuro-oncology Unit, The Royal Marsden NHS Foundation Trust, London, SW3 6JJ, UK
20
Clinical Oncology Unit, The Royal Marsden NHS Foundation Trust, London, SW3 6JJ, UK
21
Sarcoma Unit, The Royal Marsden NHS Foundation Trust, London, SW3 6JJ, UK
All rights reserved. No reuse allowed without permission.
preprint (which was not certified by peer review) is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity.
The copyright holder for thisthis version posted December 23, 2020. ; https://doi.org/10.1101/2020.12.21.20248608doi: medRxiv preprint
NOTE: This preprint reports new research that has not been certified by peer review and should not be used to guide clinical practice.

2
22
Palliative Medicine, The Royal Marsden NHS Foundation Trust, London, SW3 6JJ, UK
23
Gynaecology Unit, The Royal Marsden NHS Foundation Trust, London, SW3 6JJ, UK
24
Anaesthetics, Perioperative Medicine and Pain Department, The Royal Marsden NHS
Foundation Trust, London, SW3 6JJ, UK
25
Lung Unit, The Royal Marsden NHS Foundation Trust, London, SW3 6JJ, UK
26
Head and Neck, The Royal Marsden NHS Foundation Trust, London, SW3 6JJ, UK
27
Acute Oncology Service, The Royal Marsden NHS Foundation Trust, London, SW3 6JJ, UK
28
Neurodegeneration Biology Laboratory, The Francis Crick Institute, London, NW1 1AT, UK
29
Structural Biology of Disease Processes Laboratory, The Francis Crick Institute, London,
NW1 1AT, UK
30
Cancer Evolution and Genome Instability Laboratory, The Francis Crick Institute, London,
NW1 1AT, UK
31
Haemato-oncology Unit, The Royal Marsden NHS Foundation Trust, London, SW3 6JJ, UK
32
Division of Genetics and Epidemiology and Division of Breast Cancer Research, The
Institute of Cancer Research, London, SW7 3RP, UK
33
Worldwide Influenza Centre, The Francis Crick Institute, London, NW1 1AT, UK
34
Department of Infectious Disease, Imperial College London, W12 0NN, UK
35
The Wellcome Center for Infectious Disease Research in Africa, University Cape Town,
Cape Town, Observatory 7925, Republic of South Africa
36
Equal contributions
*correspondence to: samra.turajlic@crick.ac.uk
The CAPTURE consortium
The members of the CAPTURE consortium include Lewis Au, Susana Banerjee, Katie Bentley,
Shree Bhide, Laura Amanda Boos, Fiona Byrne, The Crick COVID19 Consortium, Ian Chau,
David Cunningham, Joanne Droney, Annika Fendler, Andrew Furness, Camille Gerard, Firza
Gronthud, Kevin Harrington, Adrian Hayday, Shaman Jhanji, Robin Jones, George Kassiotis,
Yasir Khan, Sacheen Kumar, James Larkin, Steve K.W. Leung, Michael Jones, Paula Lorgelly,
Richard Martin, Ethna McFerran, Christina Messiou, Emma Nicholson, Alicia Okines, Clare
Peckitt, Lisa Pickering, Karin Purshouse, Alison Reid, Caroline Relton, Jennifer Rusby, Scott
Shepherd, Ben Shum, Tim Slattery, Naureen Starling, Anthony Swerdlow, Stefan
Symeonides, Kate Tatham, Samra Turajlic, Nicholas Turner, Liam Welsh, Katalin Wilkinson,
Robert Wilkinson, Matthew Wheater, Kate Young, and Nadia Yousaf.
COVID-19-Crick Consortium
Titilayo Abiola, Jim Aitken, Zoe Allen, Rachel Ambler, Karen Ambrose, Emma Ashton, Alida
Avola, Samutheswari Balakrishnan, Caitlin Barns-Jenkins, Genevieve Barr, Sam Barrell,
Souradeep Basu, Rodrigo Batalha, Rupert Beale, Clare Beesley, Teresa Bertran, Natalie
Bevan, Nisha Bhardwaj, Shahnaz Bibi, Ganka Bineva-Todd, Dhruva Biswas, Michael J
Blackman, Dominique Bonnet, Carles Bosch, Faye Bowker, Malgorzata Broncel, Claire
Brooks, Michael D Buck, Andrew Buckton, Timothy Budd, Alana Burrell, Louise Busby,
Claudio Bussi, Simon Butterworth, Matthew Byott, Fiona Byrne, Richard Byrne, Simon
Caidan, Veronique Calleja, Enrica Calvani, Joanna Campbell, Johnathan C anton, Ana
Cardoso, Nick Carter, Luiz Carvalho, Raffaella Carzaniga, Antonio Casal, Natalie Chandler, Q u
Chen, Peter Cherepanov, Laura Churchward, Graham Clark, Bobbi Clayton, Clementina
Cobolli Gigli, Zena Collins, Nicola Cook, Cristina Cotobal Martin, Sally Cottrell, Margaret
Crawford, Stefania Crotta, Laura Cubitt, Tom Cullup, Annalisa D'Avola, Heledd Davies,
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Patrick Davis, Dara Davison, Joost De Folter, Vicky Dearing, Solene Debaisieux, Monica Diaz-
Romero, Alison Dibbs, Jessica Diring, Paul C Driscoll, Christopher Earl, Amelia Edwards, Chris
Ekin, Dimitrios Evangelopoulos, Todd Fallesen, Rupert Faraway, Antony Fearns, Aaron
Ferron, Efthymios Fidanis, Patricia Figuiredo-Nunes, Katja Finsterbusch, Dan Fitz, James
Fleming, Helen Flynn, Ashley Fowler, Daniel Frampton , Bruno Frederico, Alessandra Gaiba,
Anthony Gait, Steve Gamblin, Sonia Gandhi, Julian Gannon, Edmund Garr, Kathleen Gärtner,
Acely Garza-Garcia, Liam Gaul, Helen M Golding, Jacki Goldman, Robert Goldstone, Belen
Gomez Dominguez, Hui Gong, Ilaria Gori, Paul R Grant, Maria Greco, Mariana Grobler,
Anabel Guedan, Silvana Guioli, Maximiliano G Gutierrez, Fiona Hackett, Chris Hadjigeorgiou,
Ross Hall, Steinar Halldorsson, Suzanne Harris, Sugera Hashim, Emine Hatipoglu, Lyn Healy,
Judith Heaney, Susanne Herbst, Graeme Hewitt, Theresa Higgins, Prisca Hill, Steve
Hindmarsh, Rajnika Hirani, Han Ngoc Ho, Maxine Holder, Joshua Hope, Elizabeth Horton,
Beth Hoskins, Catherine F Houlihan, Michael Howell, Louise Howitt, Jacqueline Hoyle, Mint
R Htun, Michael Hubank, Hector Huerga Encabo, Deborah Hughes, Jane Hughes, Almaz
Huseynova, Ming-Shih Hwang, Fairouz Ibrahim, Rachael Instrell, Deborah Jackson, Mariam
Jamal-Hanjani, Lucy Jenkins, Ming Jiang, Mark Johnson, Leigh Jones, Neil Justin, Nnennay a
Kanu, George Kassiotis, Gavin Kelly, Geoff Kelly, Louise Kiely, Anastacio King Spert Teixeira,
Fiona Kinnis, Stuart Kirk, Svend Kjaer, Ellen Knuepfer, Nikita Komarov, Paul Kotzampaltiris,
Konstantinos Kousis, Tammy Krylova, Ania Kucharska, Robyn Labrum, Catherine Lambe,
Michelle Lappin, Stacey-Ann Lee, Andrew Levett, Lisa Levett, Marcel Levi, Nick Lewis, Hon-
Wing Liu, Shuangyan Liu, Sam Loughlin, Wei-Ting Lu, Robert Ludwig, James I MacRae,
Akshay Madoo, Sarah Manni, Julie A Marczak, Manuella Marques, Mimmi Martensson,
Thomas Martinez, Bishara Marzook, John Matthews, Joachim M Matz, Samuel McCall, Laura
E McCoy, Fiona McKay, Edel C McNamara, Sofanit Mebrate, Hilina Mehari, Manuela
Melchionda, Carlos M Minutt i, Gita Mistry, Miriam Molina-Arcas, Beatriz Montaner, Kylie
Montgomery, Catherine Moore, David Moore, Anastasia Moraiti, Raveena Morar, Luc ia
Moreira-Teixeira, Joyita Mukherjee, Cristina Naceur-Lombardelli, Eleni Nastouli, Aileen
Nelson, Jerome Nicod, Luke Nightingale, Stephanie Nofal, Paul Nurse, Savita Nutan, Anne
O'Garra, Jean D O'Leary, Olga O'Neill, Nicola O'Reilly, Caroline Oedekoven, Jessica Olsen,
Paula Ordonez Suarez, Neil Osborne, Amar Pabari, Aleksandra Pajak, Venizelos
Papayannopoulos, Stavroula M Paraskevopoulou, Namita Patel, Yogen Patel, Oana Paun,
Nigel Peat, Laura Peces-Barba Castano, Ana Perez Caballero, Jimena Perez-Lloret, Magali S
Perrault, Abigail Perrin, Roy Poh, Enzo Z Poirier, James M Polke, Marc Pollitt, Lucia Prieto-
Godino, Alize Proust, Clinda Puvirajasinghe, Val Pye, Christophe Queval, Vijaya
Ramachandran, Abhinay Ramaprasad, Peter Ratcliffe, Minoo Razi, Laura Reed, Caetano Reis
e Sousa, Kayleigh Richardson, Sophie Ridewood, Karine Rizzoti, Fiona Roberts, Rowenna
Roberts, Angela Rodgers, Pablo Romero Clavijo, Annachiara Rosa, Alice Rossi, Chloe
Roustan, Andrew Rowan, Erik Sahai, Aaron Sait, Katarzyna Sala, Emilie Sanchez, Theo
Sanderson, Pierre Santucci, Fatima Sardar, Adam Sateriale, Ji ll A Saunders, Chelsea Sawyer,
Anja Schlott, Edina Schweighoffer, Sandra Segura-Bayona, Rajvee Shah Punatar, Maryam
Shahmanesh, Joe Shaw, Gee Yen Shin, Mariana Silva Dos Santos, Margaux Silvestre,
Matthew Singer, Marie Sjothun, Daniel M Snell, Ok-Ryul Song, Christelle Soudy, Moira J
Spyer, Louisa Steel, Amy Strange, Adrienne E Sullivan, Charles Swanton, M ichele S Y Tan, Zoe
H Tautz-Davis, Raquel Taveira-Marques, Effie Taylor, Gunes Taylor, Harriet B Taylor, Alison
Taylor-Beadling, Fernanda Teixeira Subtil, Berta Terré Torras, Goran Tomic , Patrick Toolan-
Kerr, Francesca Torelli, Tea Toteva, Moritz Treeck, Hadija Trojer, Ming-Han C Tsai, James MA
Turner, Melanie Turner, Jernej Ule, Rachel Ulferts, Sharon P Vanloo, Selvaraju Veeriah, Raju
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Vousden, Andreas Wack, Claire Walder, Jane Walker, Philip A Walker, Yiran Wang, Sophia
Ward, Catharina Wenman, Luke Wiliams, Matthew J W illiams, Cherry Wong, Wai Keong
Wong, Chi Wong, Joshua Wright, Mary Wu, Lauren Wynne, Zheng Xiang, Melvyn Yap, Julian
A Zagalak, Davide Zecchin, Rachel Zillwood
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SUMMARY (144 words; max 150)
There is a pressing need to characterise the nature, extent and duration of immune
response to SARS-CoV-2 in cancer patients and inform risk-reduction strategies and
preserve cancer outcomes. CAPTURE is a prospective, longitudinal cohort study of cancer
patients and healthcare workers (HCWs) integrating longitudinal immune profiling and
clinical annotation. We evaluated 529 blood samples and 1051 oronasopharyngeal swabs
from 144 cancer patients and 73 HCWs and correlated wi th >200 clinical variables. In
patients with solid cancers and HCWs, S1-reactive and neutralising antibodies to SARS-CoV-2
were detectable f ive months post-infection. SARS-CoV-2-specific T-cell responses were
detected, and CD4
+
T-cel l responses correlated with S1 antibody levels. Patients with
haematological malignancies had impaired but partially compensated immune responses.
Overall, cancer stage, disease status, and therapies did not correlate with immune
responses. These findings have implications for understanding individual risks and potential
effectiveness of SARS-CoV-2 vaccination in the cancer population.
KEYWORDS (up to 10)
SARS-CoV-2, COVID-19, Cancer, Adaptive Immunity, Antibody Response, Neutralising
Antibodies, T-cell Response, Prospective Study, Vaccine
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The copyright holder for thisthis version posted December 23, 2020. ; https://doi.org/10.1101/2020.12.21.20248608doi: medRxiv preprint

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Q1. What are the contributions mentioned in the paper "Adaptive immunity to sars-cov-2 in cancer patients: the capture study" ?

For example, this paper showed that SARS-CoV-2 infection results in an antibody response to major antigens ( spike and spike ) in cancer patients.