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1. Sensitive Detection of SARS-CoV-2-Specific Antibodies in Dried Blood Spot Samples

Author

Morley, Gabriella L., Taylor, Stephen, Jossi, Sian, Perez-Toledo, Marisol, Faustini, Sian E., Marcial-Juarez, Edith, Shields, Adrian M., Goodall, Margaret, Allen, Joel D., Watanabe, Yasunori, Newby, Maddy L., Crispin, Max, Drayson, Mark T., Cunningham, Adam F., Richter, Alex G., and OShea, Matthew K.

Subjects
Blood -- Medical examination, Serodiagnosis -- Methods, Health
Abstract

A confirmed diagnosis of acute coronavirus disease (COVID-19) depends on the detection of RNA from the causative pathogen, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In contrast, although serologic testing [...]

Published
2020
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2. SARS-CoV-2 infection is associated with anti-desmoglein 2 autoantibody detection

Author

Ward, Kerensa E, primary, Steadman, Lora, additional, Karim, Abid R, additional, Reynolds, Gary M, additional, Pugh, Matthew, additional, Chua, Winnie, additional, Faustini, Sian E, additional, Veenith, Tonny, additional, Thwaites, Ryan S, additional, Openshaw, Peter J M, additional, Drayson, Mark T, additional, Shields, Adrian M, additional, Cunningham, Adam F, additional, Wraith, David C, additional, and Richter, Alex G, additional

Published
2023
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4. Impact of vaccination on hospitalization and mortality from COVID-19 in patients with primary and secondary immunodeficiency: The United Kingdom experience

Author

Shields, Adrian M., primary, Tadros, Susan, additional, Al-Hakim, Adam, additional, Nell, Jeremy M., additional, Lin, Me Me Nay, additional, Chan, Michele, additional, Goddard, Sarah, additional, Dempster, John, additional, Dziadzio, Magdalena, additional, Patel, Smita Y., additional, Elkalifa, Shuayb, additional, Huissoon, Aarnoud, additional, Duncan, Christopher J. A., additional, Herwadkar, Archana, additional, Khan, Sujoy, additional, Bethune, Claire, additional, Elcombe, Suzanne, additional, Thaventhiran, James, additional, Klenerman, Paul, additional, Lowe, David M., additional, Savic, Sinisa, additional, Burns, Siobhan O., additional, and Richter, Alex G., additional

Published
2022
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5. Vitamin D status: a U-shaped relationship for SARS-CoV-2 seropositivity in UK healthcare workers

Author

Lugg, Sebastian T, primary, Mackay, William R, additional, Faniyi, Aduragbemi A, additional, Faustini, Sian E, additional, Webster, Craig, additional, Duffy, Joanne E, additional, Hewison, Martin, additional, Shields, Adrian M, additional, Parekh, Dhruv, additional, Richter, Alex G, additional, Scott, Aaron, additional, and Thickett, David R, additional

Published
2022
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6. SARS-CoV-2 Spike- and Nucleoprotein-Specific Antibodies Induced After Vaccination or Infection Promote Classical Complement Activation

Author

Lamerton, Rachel E., primary, Marcial-Juarez, Edith, additional, Faustini, Sian E., additional, Perez-Toledo, Marisol, additional, Goodall, Margaret, additional, Jossi, Siân E., additional, Newby, Maddy L., additional, Chapple, Iain, additional, Dietrich, Thomas, additional, Veenith, Tonny, additional, Shields, Adrian M., additional, Harper, Lorraine, additional, Henderson, Ian R., additional, Rayes, Julie, additional, Wraith, David C., additional, Watson, Steve P., additional, Crispin, Max, additional, Drayson, Mark T., additional, Richter, Alex G., additional, and Cunningham, Adam F., additional

Published
2022
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7. SARS‐CoV‐2‐specific IgG1/IgG3 but not IgM in children with Pediatric Inflammatory Multi‐System Syndrome

Author

Perez‐toledo, Marisol, Faustini, Sian E., Jossi, Sian E., Shields, Adrian M., Marcial‐juarez, Edith, Kanthimathinathan, Hari Krishnan, Allen, Joel D., Watanabe, Yasunori, Goodall, Margaret, Willcox, Benjamin E., Willcox, Carrie R., Salim, Mahboob, Wraith, David C., Veenith, Tonny V., Syrimi, Eleni, Drayson, Mark T., Jyothish, Deepthi, Al‐abadi, Eslam, Chikermane, Ashish, Welch, Steven B., Masilamani, Kavitha, Hackett, Scott, Crispin, Max, Scholefield, Barnaby R., Cunningham, Adam F., Richter, Alex G., and Genuneit, Jon

Subjects
2019-20 coronavirus outbreak, biology, Coronavirus disease 2019 (COVID-19), business.industry, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Immunology, medicine.disease, Virology, Immunoglobulin G, Systemic inflammatory response syndrome, Immunoglobulin M, Pediatrics, Perinatology and Child Health, biology.protein, Immunology and Allergy, Medicine, business, Letters to the Editor, Letter to the Editor
Abstract

During the COVID-19 outbreak, reports have surfaced of children who present with features of a multisystem inflammatory syndrome with overlapping features of Kawasaki disease and toxic shock syndrome - Paediatric Inflammatory Multisystem Syndrome- temporally associated with SARS-CoV-2 pandemic (PIMS-TS). Initial reports find that many of the children are PCR-negative for SARS-CoV-2, so it is difficult to confirm whether this syndrome is a late complication of viral infection in an age group largely spared the worst consequences of this infection, or if this syndrome reflects enhanced surveillance.Children hospitalised for symptoms consistent with PIMS-TS between 28 April and 8 May 2020, and who were PCR-negative for SARS-CoV-2, were tested for antibodies to viral spike glycoprotein using an ELISA test.Eight patients (age range 7-14 years, 63% male) fulfilled case-definition for PIMS-TS during the study period. Six of the eight patients required admission to intensive care. All patients exhibited significant IgG and IgA responses to viral spike glycoprotein. Further assessment showed that the IgG isotypes detected in children with PIMS-TS were of the IgG1 and IgG3 subclasses, a distribution similar to that observed in samples from hospitalised adult COVID-19 patients. In contrast, IgG2 and IgG4 were not detected in children or adults. IgM was not detected in children, which contrasts with adult hospitalised adult COVID-19 patients of whom all had positive IgM responses.Strong IgG antibody responses can be detected in PCR-negative children with PIMS-TS. The low detection rate of IgM in these patients is consistent with infection having occurred weeks previously and that the syndrome onset occurs well after the control of SARS-CoV-2 viral load. This implies that the disease is largely immune-mediated. Lastly, this indicates that serology can be an appropriate diagnostic tool in select patient groups.

Published
2021

8. Outcomes following SARS-CoV-2 infection in patients with primary and secondary immunodeficiency in the UK

Author

Shields, Adrian M, primary, Anantharachagan, Ariharan, additional, Arumugakani, Gururaj, additional, Baker, Kenneth, additional, Bahal, Sameer, additional, Baxendale, Helen, additional, Bermingham, William, additional, Bhole, Malini, additional, Boules, Evon, additional, Bright, Philip, additional, Chopra, Charu, additional, Cliffe, Lucy, additional, Cleave, Betsy, additional, Dempster, John, additional, Devlin, Lisa, additional, Dhalla, Fatima, additional, Diwakar, Lavanya, additional, Drewe, Elizabeth, additional, Duncan, Christopher, additional, Dziadzio, Magdalena, additional, Elcombe, Suzanne, additional, Elkhalifa, Shuayb, additional, Gennery, Andrew, additional, Ghanta, Harichandrana, additional, Goddard, Sarah, additional, Grigoriadou, Sofia, additional, Hackett, Scott, additional, Hayman, Grant, additional, Herriot, Richard, additional, Herwadkar, Archana, additional, Huissoon, Aarnoud, additional, Jain, Rashmi, additional, Jolles, Stephen, additional, Johnston, Sarah, additional, Khan, Sujoy, additional, Laffan, James, additional, Lane, Peter, additional, Leeman, Lucy, additional, Lowe, David M, additional, Mahabir, Shanti, additional, Lochlainn, Dylan James Mac, additional, McDermott, Elizabeth, additional, Misbah, Siraj, additional, Moghaddas, Fiona, additional, Morsi, Hadeil, additional, Murng, Sai, additional, Noorani, Sadia, additional, O’Brien, Rachael, additional, Patel, Smita, additional, Price, Arthur, additional, Rahman, Tasneem, additional, Seneviratne, Suranjith, additional, Shrimpton, Anna, additional, Stroud, Catherine, additional, Thomas, Moira, additional, Townsend, Katie, additional, Vaitla, Prashantha, additional, Verma, Nisha, additional, Williams, Anthony, additional, Burns, Siobhan O, additional, Savic, Sinisa, additional, and Richter, Alex G, additional

Published
2022
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9. SARS-CoV-2 vaccine responses following CD20-depletion treatment in patients with haematological and rheumatological disease: a West Midlands Research Consortium study

Author

Shields, Adrian M, primary, Venkatachalam, Srinivasan, additional, Shafeek, Salim, additional, Paneesha, Shankara, additional, Ford, Mark, additional, Sheeran, Tom, additional, Kelly, Melanie, additional, Qureshi, Iman, additional, Salhan, Beena, additional, Karim, Farheen, additional, De Silva, Neelakshi, additional, Stones, Jacqueline, additional, Lee, Sophie, additional, Khawaja, Jahanzeb, additional, Kaudlay, Praveen Kumar, additional, Whitmill, Richard, additional, Kakepoto, Ghulam Nabi, additional, Parry, Helen M, additional, Moss, Paul, additional, Faustini, Sian E, additional, Richter, Alex G, additional, Drayson, Mark T, additional, and Basu, Supratik, additional

Published
2021
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10. Vaccine Efficacy after Rituximab Exposure: First Interim Analysis of Virtue Project on Behalf of West Midlands Research Consortium, UK

Author

Shields, Adrian M, primary, Venkatachalam, Srinivasan, additional, Paneesha, Shankara, additional, Ford, Mark, additional, Sheeran, Tom, additional, Kelly, Melanie, additional, Karim, Farheen, additional, Qureshi, Iman, additional, Salhan, Beena, additional, DeSilva, Neelakshi, additional, Stones, Jacqueline, additional, Lee, Sophie, additional, Khawaja, Jahanzeb, additional, Kaudlay, Praveen Kumar, additional, Whitmill, Richard, additional, Nabikakepoto, Ghulam, additional, Faustini, Sian E, additional, Richter, Alex G, additional, Drayson, Mark T, additional, and Basu, Supratik, additional

Published
2021
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11. Serological responses to SARS-CoV-2 following non-hospitalised infection: clinical and ethnodemographic features associated with the magnitude of the antibody response

Author

Shields, Adrian M, primary, Faustini, Sian E, additional, Perez-Toledo, Marisol, additional, Jossi, Sian, additional, Allen, Joel D, additional, Al-Taei, Saly, additional, Backhouse, Claire, additional, Dunbar, Lynsey A, additional, Ebanks, Daniel, additional, Emmanuel, Beena, additional, Faniyi, Aduragbemi A, additional, Garvey, Mark, additional, Grinbergs, Annabel, additional, McGinnell, Golaleh, additional, O'Neill, Joanne, additional, Watanabe, Yasunori, additional, Crispin, Max, additional, Wraith, David C, additional, Cunningham, Adam F, additional, Drayson, Mark T, additional, and Richter, Alex G, additional

Published
2021
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12. Establishing the prevalence of common tissue-specific autoantibodies following severe acute respiratory syndrome coronavirus 2 infection

Author

Richter, Alex G, primary, Shields, Adrian M, additional, Karim, Abid, additional, Birch, David, additional, Faustini, Sian E, additional, Steadman, Lora, additional, Ward, Kerensa, additional, Plant, Timothy, additional, Reynolds, Gary, additional, Veenith, Tonny, additional, Cunningham, Adam F, additional, Drayson, Mark T, additional, and Wraith, David C, additional

Published
2021
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13. Development of a high‐sensitivity ELISA detecting IgG, IgA and IgM antibodies to the SARS‐CoV‐2 spike glycoprotein in serum and saliva

Author

Faustini, Sian E., primary, Jossi, Sian E., additional, Perez‐Toledo, Marisol, additional, Shields, Adrian M., additional, Allen, Joel D., additional, Watanabe, Yasunori, additional, Newby, Maddy L., additional, Cook, Alex, additional, Willcox, Carrie R., additional, Salim, Mahboob, additional, Goodall, Margaret, additional, Heaney, Jennifer L., additional, Marcial‐Juarez, Edith, additional, Morley, Gabriella L., additional, Torlinska, Barbara, additional, Wraith, David C., additional, Veenith, Tonny V., additional, Harding, Stephen, additional, Jolles, Stephen, additional, Ponsford, Mark J., additional, Plant, Tim, additional, Huissoon, Aarnoud, additional, O'Shea, Matthew K., additional, Willcox, Benjamin E., additional, Drayson, Mark T., additional, Crispin, Max, additional, Cunningham, Adam F., additional, and Richter, Alex G., additional

Published
2021
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14. Increased Seroprevalence and Improved Antibody Responses Following Third Primary SARS-CoV-2 Immunisation: An Update From the COV-AD Study.

Author

Shields, Adrian M., Faustini, Sian E., Hill, Harriet J., Al-Taei, Saly, Tanner, Chloe, Ashford, Fiona, Workman, Sarita, Moreira, Fernando, Verma, Nisha, Wagg, Hollie, Heritage, Gail, Campton, Naomi, Stamataki, Zania, Drayson, Mark T., Klenerman, Paul, Thaventhiran, James E. D., Elkhalifa, Shuayb, Goddard, Sarah, Johnston, Sarah, and Huissoon, Aarnoud

Subjects
ANTIBODY formation, PRIMARY immunodeficiency diseases, SARS-CoV-2, COVID-19 vaccines, IMMUNIZATION
Abstract

Background: Patients with primary and secondary antibody deficiency are vulnerable to COVID-19 and demonstrate diminished responses following two-dose SARS-CoV-2 vaccine schedules. Third primary vaccinations have been deployed to enhance their humoral and cellular immunity. Objectives: To determine the immunogenicity of the third primary SARS-CoV-2 immunisation in a heterogeneous cohort of patients with antibody deficiency. Methods: Participants enrolled in the COV-AD study were sampled before and after their third vaccine dose. Serological and cellular responses were determined using ELISA, livevirus neutralisation and ELISPOT assays. Results: Following a two-dose schedule, 100% of healthy controls mounted a serological response to SARS-CoV-2 vaccination, however, 38.6% of individuals with antibody deficiency remained seronegative. A third primary SARS-CoV-2 vaccine significantly increased anti-spike glycoprotein antibody seroprevalence from 61.4% to 76.0%, the magnitude of the antibody response, its neutralising capacity and induced seroconversion in individuals who were seronegative after two vaccine doses. Vaccine-induced serological responses were broadly cross-reactive against the SARS-CoV-2 B.1.1.529 variant of concern, however, seroprevalence and antibody levels remained significantly lower than healthy controls. No differences in serological responses were observed between individuals who received AstraZeneca ChAdOx1 nCoV-19 and Pfizer BioNTech 162b2 during their initial two-dose vaccine schedule. SARS-CoV-2 infectionnaive participants who had received a heterologous vaccine as a third dose were significantly more likely to have a detectable T cell response following their third vaccine dose (61.5% vs 11.1%). Conclusion: These data support the widespread use of third primary immunisations to enhance humoral immunity against SARS-CoV-2 in individuals with antibody deficiency. [ABSTRACT FROM AUTHOR]

Published
2022
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16. T cell response to SARS-CoV-2 infection in humans: A systematic review

Author

Shrotri, Madhumita, primary, van Schalkwyk, May C. I., additional, Post, Nathan, additional, Eddy, Danielle, additional, Huntley, Catherine, additional, Leeman, David, additional, Rigby, Samuel, additional, Williams, Sarah V., additional, Bermingham, William H., additional, Kellam, Paul, additional, Maher, John, additional, Shields, Adrian M., additional, Amirthalingam, Gayatri, additional, Peacock, Sharon J., additional, and Ismail, Sharif A., additional

Published
2021
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17. Antibody response to SARS-CoV-2 infection in humans: A systematic review

Author

Post, Nathan, primary, Eddy, Danielle, additional, Huntley, Catherine, additional, van Schalkwyk, May C. I., additional, Shrotri, Madhumita, additional, Leeman, David, additional, Rigby, Samuel, additional, Williams, Sarah V., additional, Bermingham, William H., additional, Kellam, Paul, additional, Maher, John, additional, Shields, Adrian M., additional, Amirthalingam, Gayatri, additional, Peacock, Sharon J., additional, and Ismail, Sharif A., additional

Published
2020
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18. SARS-CoV-2 vaccine responses following CD20-depletion treatment in patients with haematological and rheumatological disease: a West Midlands Research Consortium study.

Author

Shields, Adrian M, Venkatachalam, Srinivasan, Shafeek, Salim, Paneesha, Shankara, Ford, Mark, Sheeran, Tom, Kelly, Melanie, Qureshi, Iman, Salhan, Beena, Karim, Farheen, De Silva, Neelakshi, Stones, Jacqueline, Lee, Sophie, Khawaja, Jahanzeb, Kaudlay, Praveen Kumar, Whitmill, Richard, Kakepoto, Ghulam Nabi, Parry, Helen M, Moss, Paul, and Faustini, Sian E

Subjects
*VACCINE effectiveness, *COVID-19 vaccines, *BOOSTER vaccines, *CONSORTIA, *B cells, *IMMUNE reconstitution inflammatory syndrome, *AUTOIMMUNE diseases
Abstract

B-cell-depleting agents are among the most commonly used drugs to treat haemato-oncological and autoimmune diseases. They rapidly induce a state of peripheral B-cell aplasia with the potential to interfere with nascent vaccine responses, particularly to novel antigens. We have examined the relationship between B-cell reconstitution and SARS-CoV-2 vaccine responses in two cohorts of patients previously exposed to B-cell-depleting agents: a cohort of patients treated for haematological B-cell malignancy and another treated for rheumatological disease. B-cell depletion severely impairs vaccine responsiveness in the first 6 months after administration: SARS-CoV-2 antibody seroprevalence was 42.2% and 33.3% in the haemato-oncological patients and rheumatology patients, respectively and 22.7% in patients vaccinated while actively receiving anti-lymphoma chemotherapy. After the first 6 months, vaccine responsiveness significantly improved during early B-cell reconstitution; however, the kinetics of reconstitution was significantly faster in haemato-oncology patients. The AstraZeneca ChAdOx1 nCoV-19 vaccine and the Pfizer BioNTech 162b vaccine induced equivalent vaccine responses; however, shorter intervals between vaccine doses (<1 m) improved the magnitude of the antibody response in haeamto-oncology patients. In a subgroup of haemato-oncology patients, with historic exposure to B-cell-depleting agents (>36 m previously), vaccine non-responsiveness was independent of peripheral B-cell reconstitution. The findings have important implications for primary vaccination and booster vaccination strategies in individuals clinically vulnerable to SARS-CoV-2. B cell depleting drugs including rituximab are commonly used to treat haematological malignancy and autoimmune diseases but may impair the immunological response to vaccination. This study investigates SARS-CoV-2 vaccine responses in individuals with haematological and rheumatological disease with previously exposure to B cell depleting agents. Vaccination within the first 6 months of B cell depletion is associated with significant impairment of vaccine responsiveness; however, rheumatology and haemato-oncological patients display different kinetics of B cell reconstitution corresponding to differential vaccine responsiveness over time. [ABSTRACT FROM AUTHOR]

Published
2022
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20. Classical and Non-classical Presentations of Complement Factor I Deficiency: Two Contrasting Cases Diagnosed via Genetic and Genomic Methods

Author

Shields, Adrian M., Pagnamenta, Alistair T., Pollard, Andrew J., Taylor, Jenny C., Allroggen, Holger, and Patel, Smita Y.

Subjects
genomic medicine, complement deficiency, Immunology, complement factor I, pneumococcal infection, Case Report, primary immunodeficiency, neuroinflammation
Abstract

Deficiency of complement factor I is a rare immunodeficiency that typically presents with increased susceptibility to encapsulated bacterial infections. However, non-infectious presentations including rheumatological, dermatological and neurological disease are increasingly recognized and require a high-index of suspicion to reach a timely diagnosis. Herein, we present two contrasting cases of complement factor I deficiency: one presenting in childhood with invasive pneumococcal disease, diagnosed using conventional immunoassays and genetics and the second presenting in adolescence with recurrent sterile neuroinflammation, diagnosed via a genomic approach. Our report and review of the literature highlight the wide spectrum of clinical presentations associated with CFI deficiency and the power of genomic medicine to inform rare disease diagnoses.

Published
2019

24. Right ventricular metastasis of transitional cell carcinoma of the renal pelvis: successful single stage surgical treatment.

Author

Shields, Adrian M, Pomplun, Sabine, Deshpande, Ranjit, and Whitaker, Donald C

Abstract

A 58-year-old female presented with symptoms mimicking infective endocarditis and was diagnosed with a right ventricular metastasis from a transitional cell carcinoma (TCC) of the left renal pelvis. The patient was treated with concurrent removal of the cardiac tumour and radical left nephrectomy followed by adjuvant gemcitabine-cisplatin chemotherapy. To our knowledge, this is the 14th report of cardiac metastases from TCC and the only case where one-stage surgical management of primary and cardiac metastases from TCC has been successfully completed.

Published
2011
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25. Improved monitoring of clinical response in Systemic Lupus Erythematosus by longitudinal trend in soluble vascular cell adhesion molecule-1

Author

Lewis, Myles J., Vyse, Simon, Shields, Adrian M., Zou, Lu, Khamashta, Munther, Gordon, Patrick A., Pitzalis, Costantino, Vyse, Timothy J., and D’Cruz, David P.

Subjects
Adult, Male, Plasma cells, Vascular cell adhesion molecule-1, Biomarker, Complement C3, Middle Aged, Memory B cells, Cohort Studies, Treatment Outcome, Soluble cell adhesion molecules, Systemic lupus erythematosus, CD95, Humans, Lupus Erythematosus, Systemic, Female, Longitudinal Studies, Anti-double-stranded DNA antibodies, Plasmablasts, skin and connective tissue diseases, Biomarkers, Research Article, Monitoring, Physiologic
Abstract

Background To determine whether optimal use of serial measurements of serum levels of soluble cell adhesion molecules (CAM) can improve monitoring of disease activity in SLE. Methods Serum levels of soluble CAM and conventional SLE biomarkers were measured in serial samples (n = 80) from 21 SLE patients during and after flare and correlated in longitudinal analysis with disease activity determined by ECLAM score. Blood samples from a second cohort of 34 SLE patients were subject to flow cytometry to correlate serum biomarkers with B cell subsets. Results By adjusting for the baseline level (at the first visit), delta soluble vascular cell adhesion molecule-1 (sVCAM-1) showed stronger correlation with changes in ECLAM score and improved sensitivity and specificity for identifying SLE responders versus non-responders compared to conventional SLE biomarkers including anti-dsDNA antibody titre and complement C3. Multiple regression analysis identified delta sVCAM-1 as the best marker of SLE clinical response. sVCAM-1 levels were significantly correlated with CD95+CD27+ activated memory B cells, CD95+ plasmablasts and circulating plasma cell numbers in SLE patients. Conclusion Subtracting a baseline level of sVCAM-1 for each individual substantially improved its utility as a biomarker. Delta sVCAM-1 was superior to conventional SLE biomarkers for monitoring changes in disease activity. This suggests that serial monitoring of serum sVCAM-1 trends should be considered in SLE patients to document responses to treatment. We hypothesise that the correlation between activated B cell subsets and circulating plasma cell numbers with soluble VCAM-1 serum levels in SLE may relate to the important role of VCAM-1 in B lymphocyte survival and maturation in bone marrow and secondary lymphoid tissues. Electronic supplementary material The online version of this article (doi:10.1186/s13075-015-0896-7) contains supplementary material, which is available to authorized users.

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